Affinage

RAB27A

Ras-related protein Rab-27A · UniProt P51159

Length
221 aa
Mass
24.9 kDa
Annotated
2026-06-10
100 papers in source corpus 54 papers cited in narrative 54 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAB27A is a GTP-regulated small GTPase that serves as a master organizer of regulated secretory and organelle-transport pathways, recruiting cell-type-specific effectors in its GTP-bound state to drive the docking and exocytosis of diverse secretory organelles (PMID:14617806, PMID:19966785). Its biological importance is established by loss-of-function mutations that cause Griscelli syndrome type 2, with patient cells showing defective cytotoxic granule exocytosis (PMID:10835631), and by the ashen mouse, in which Rab27a deficiency disrupts melanosome transport and platelet dense-granule biology (PMID:10859366). Effector engagement requires switch-region residues, and Griscelli mutations either disrupt GTP binding/folding or selectively abolish effector interaction while preserving GTPase activity (e.g., Trp73Gly, G43S) (PMID:12446441, PMID:18397837), a specificity rooted in Rab27-unique structural contacts mapped crystallographically with the Slac2-a effector domain (PMID:18940604). In melanocytes RAB27A on melanosomes recruits melanophilin/Slac2-a, which simultaneously binds myosin Va to form a tripartite Rab27a-melanophilin-myosin Va transport complex driving peripheral melanosome dispersion (PMID:11266470, PMID:11856727, PMID:12062444), and additionally recruits SPIRE1 with formin-1 to assemble the actin tracks for this long-range movement (PMID:32661310). The same GTP-dependent recruitment logic operates across tissues using distinct effectors: Munc13-4 mediates lytic-granule and platelet dense-granule secretion and acts downstream of Rab27a in lymphocytes (PMID:14699162, PMID:19704116); granuphilin/Slp4-a, Slp2-a, MyRIP, JFC1/Slp1, Noc2 and Slp5 govern insulin-granule, Weibel-Palade body, azurophilic-granule and other secretory steps (PMID:11865063, PMID:15543135, PMID:19270261, PMID:17090228, PMID:27927751); and separation-of-function mutations show that Munc13-4 and melanophilin bind topologically distinct interfaces on Rab27a, explaining immunodeficiency-without-albinism phenotypes (PMID:25312756, PMID:33362801). RAB27A also controls multivesicular endosome docking at the plasma membrane to drive exosome secretion (PMID:19966785), with its nucleotide cycling (GEF MADD/DENN, GAP EPI64) and prenylation (REP-1-dependent geranylgeranylation) tuning effector occupancy and activity (PMID:7592656, PMID:16923811, PMID:23702376). RAB27A protein levels are stabilized against proteasomal degradation by KIBRA and its expression is induced transcriptionally by IRF-1 (PMID:30967557, PMID:29059701).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1995 High

    Established that Rab27 has a built-in dependence on a specific prenylation machinery, defining how the GTPase is membrane-targeted and linking it to a disease pathway before its function was known.

    Evidence In vitro prenylation with purified Rab GGTase and REP-1/REP-2, plus unprenylated protein purified from choroideremia lymphoblasts

    PMID:7592656

    Open questions at the time
    • Did not establish the cellular processes Rab27 controls
    • Functional consequence of prenylation defect on specific secretory pathways not addressed
  2. 2000 High

    Connected RAB27A genetically and functionally to two distinct human/mouse phenotypes, revealing it as a shared component of organelle-specific trafficking in immune cells, melanocytes and platelets.

    Evidence Human genetics of Griscelli syndrome type 2 with patient T-cell cytotoxicity assays, and positional cloning of the ashen mouse with BAC rescue and platelet assays

    PMID:10835631 PMID:10859366

    Open questions at the time
    • Molecular effectors mediating the trafficking not yet identified
    • Mechanism of granule docking versus polarization not resolved
  3. 2001 High

    Defined the precise secretory step Rab27a controls—membrane docking of secretory organelles—and showed it operates at the melanosome and the immunological synapse, with rescue in patient cells proving causality.

    Evidence CTL secretion/EM in ashen and gunmetal mice; melanosome IF, DN mutants and Co-IP showing myosin Va recruitment; functional rescue in patient melanocytes

    PMID:11266470 PMID:11266472 PMID:11266474

    Open questions at the time
    • Direct effector bridging Rab27a to myosin Va not yet identified
    • Mechanism distinguishing docking from fusion unresolved
  4. 2002 High

    Identified the effector logic of Rab27a: GTP-dependent recruitment of a family of SHD-containing effectors (melanophilin, granuphilin, MyRIP, Slp5, JFC1) that bridge the GTPase to motors, membranes and the secretory apparatus across multiple cell types.

    Evidence Y2H, in vitro binding, cosedimentation and Co-IP defining the Rab27a-melanophilin-myosin Va tripartite complex, granuphilin on insulin granules, MyRIP/Slp5 binding; transgenic isoform rescue and missense-mutation biochemistry

    PMID:11856727 PMID:11865063 PMID:11980908 PMID:12006666 PMID:12051743 PMID:12062444 PMID:12122117 PMID:12221080 PMID:12446441

    Open questions at the time
    • Structural basis for Rab27-versus-Rab3 effector selectivity not yet defined
    • Whether distinct effectors use distinct surfaces of Rab27a unknown
  5. 2003 High

    Generalized Rab27a's role beyond melanocytes/CTLs to regulated exocytosis in broad secretory cell types and added Munc13-4 as a platelet dense-granule effector, broadening the cell-biological scope.

    Evidence EGFP-Rab27a knock-in expression profiling with ashen rescue; affinity purification of Munc13-4 from platelets with secretion rescue; siRNA in beta cells implicating MyRIP/cortical actin

    PMID:14517322 PMID:14617806 PMID:14699162

    Open questions at the time
    • How each effector is selected in a given cell type not resolved
    • Relationship between cortical actin tethering and fusion competence unclear
  6. 2006 High

    Established the nucleotide-cycle regulators of Rab27a—EPI64 as a specific GAP—and showed that GTP-bound Rab27a constitutively populates resting platelets, framing how its activity state is set and modulated.

    Evidence TBC-protein screen with in vitro GAP assay and catalytic mutagenesis; nucleotide TLC and pulldown in platelets with GppNHp secretion assay; cooperative docking analysis with Rab3A by TIRF

    PMID:16684812 PMID:16880209 PMID:16923811

    Open questions at the time
    • GEF for Rab27a not yet identified at this stage
    • Whether GTP hydrolysis is required for fusion versus docking left ambiguous
  7. 2007 High

    Extended Rab27a's tethering function to endothelial Weibel-Palade bodies, neutrophil azurophilic granules and RPE melanosomes, showing it can both promote and restrain secretion by anchoring organelles to cortical actin.

    Evidence siRNA and knockout/mutant models with VWF multimer/flow assays, MPO secretion assays, live-cell imaging of RPE melanosomes, and Slac2-a/MyRIP/melanophilin domain analyses

    PMID:17090228 PMID:17311845 PMID:17451552 PMID:17698919 PMID:19270261

    Open questions at the time
    • Molecular switch between positive and negative regulation per cell type unresolved
    • Slow Rab27a membrane exchange mechanism not mechanistically explained
  8. 2008 High

    Provided the structural basis for Rab27 effector specificity and mapped Griscelli switch-region mutations to effector engagement, explaining why specific residues are essential for function.

    Evidence Crystal structure of Rab27B-GTP with Slac2-a effector domain plus gain-of-function chimera into Rab3A; G43S switch-I mutant cellular and Co-IP analysis; beta-cell electrophysiology in ashen cells

    PMID:18397837 PMID:18801842 PMID:18940604

    Open questions at the time
    • Whether all effectors share the same structural interface not fully resolved
    • Downstream machinery generating the releasable pool not identified
  9. 2009 High

    Resolved that Rab27a and Rab27b cover distinct steps of exosome secretion and that Rab27a acts upstream of Munc13-4 in lytic-granule maturation, ordering the pathway.

    Evidence RNAi screen with MVE EM and effector epistasis (exosomes); receptor-specific NK-cell stimulation with patient cells; TIRF imaging of azurophilic granules in single/double knockouts

    PMID:19704116 PMID:19966785 PMID:20028487

    Open questions at the time
    • How upstream signals choose Rab27a versus Munc13-4 recruitment unclear
    • Cargo determinants of distinct exosome subsets not defined
  10. 2010 High

    Demonstrated through natural separation-of-function mutations that Rab27a presents distinct binding interfaces for different effectors, accounting for tissue-selective disease manifestations.

    Evidence Biochemical GTPase/effector-binding analysis of K22R and I44T GS-2 mutants across multiple effectors; ashen-based phagocytosis and HCMV assembly loss-of-function studies

    PMID:20370853 PMID:21169636 PMID:21170347

    Open questions at the time
    • Complete residue-level map of all effector interfaces incomplete
    • Mechanism of Rab27a action in phagocytosis/viral assembly only partially defined
  11. 2012 High

    Formalized an effector-competition model in which the ratio of positive (Slp4-a) to negative (MyRIP) effectors occupying Rab27a sets organelle release probability, unifying its dual regulatory behavior.

    Evidence siRNA and overexpression of Slp4-a/MyRIP with live imaging of WPB exocytosis and Rab27A cytosol-membrane cycling

    PMID:22898601

    Open questions at the time
    • What governs effector competition stoichiometry in vivo unknown
    • Generalizability of the competition model to other organelles untested here
  12. 2013 High

    Identified MADD/DENN as the Rab27 GEF and revealed opposing Rab27a versus Rab27b pathway roles in mast cells, completing the nucleotide-cycle regulatory picture and exposing branch-specific functions.

    Evidence Antibody inhibition of MADD in permeabilized acinar cells with GTP-Rab27 measurement; five-mouse-model degranulation/F-actin analysis defining Rab27a/Mlph/MyoVa as inhibitory

    PMID:23281710 PMID:23702376

    Open questions at the time
    • MADD GEF role beyond acinar cells not established
    • How a single GTPase produces opposing outputs via different effectors not fully mechanistically resolved
  13. 2014 High

    Showed that Rab27a nucleotide cycling, not merely GTP-loading, is essential for generating the immediately releasable granule pool, and mapped a Munc13-4-specific binding site distinct from melanophilin's.

    Evidence EPI64A/Rab3GAP-driven GDP-locking with membrane capacitance in beta cells; human GS-2 R141/Y159/S163 separation-of-function mutations

    PMID:24909540 PMID:25312756

    Open questions at the time
    • Molecular event coupling Rab27a cycling to pool refilling unidentified
    • Spatial organization of the two effector sites not structurally resolved
  14. 2015 High

    Extended Rab27a function to lipid-based membrane identity, showing it delivers PI4KIIalpha-positive endosomes to control plasma-membrane phosphoinositide levels and HIV-1 assembly via Slp effectors.

    Evidence siRNA in CD4+ T cells/macrophages, live imaging of PI4KIIalpha trafficking, PI(4,5)P2 measurement, effector screen and HIV-1 assembly assays

    PMID:25940347

    Open questions at the time
    • Direct link between phosphoinositide control and other secretory pathways unexplored
    • Whether this PI pathway operates outside T cells/macrophages unknown
  15. 2016 High

    Defined Noc2 as a dual Rab2a/Rab27a effector ordering granule maturation versus late exocytosis and characterized a partial dominant-negative A87P mutation in NK-cell HLH pathogenesis.

    Evidence GTP-dependent Co-IP, mutant dissection and RNAi with insulin secretion/proinsulin processing; lentiviral A87P NK-92 cells with PLA and degranulation assays

    PMID:26880764 PMID:27927751

    Open questions at the time
    • How Rab27a is positioned relative to maturation machinery not fully resolved
    • Quantitative threshold for dominant-negative effect in patients undefined
  16. 2019 High

    Identified post-translational and functional control points of Rab27a—KIBRA-mediated protection from proteasomal degradation and a pro-invasive exosome biogenesis role—linking its abundance to disease-relevant secretion.

    Evidence Co-IP, ubiquitination assay, KIBRA-KO mouse and EM (stability); melanoma knockdown with 3D invasion, in vivo metastasis and exosome rescue/proteome analysis

    PMID:30556600 PMID:30967557

    Open questions at the time
    • E3 ligase targeting Rab27a for degradation not identified
    • Molecular cargo making exosomes pro-invasive not defined
  17. 2020 High

    Completed the melanosome model by identifying SPIRE1 as a Rab27a effector that builds actin tracks alongside the myosin-Va motor, showing Rab27a coordinates both motor and track on one organelle.

    Evidence Effector identification, genetic epistasis among SPIRE1/formin-1/melanophilin, and live imaging of melanosome transport; additional GS-2 V143A separation-of-function mapping

    PMID:32661310 PMID:33362801

    Open questions at the time
    • Spatial/temporal coordination of motor and track assembly on the melanosome not resolved
    • Whether SPIRE1-type effectors operate at other Rab27a organelles unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single GTPase integrates competing effectors, nucleotide-cycle inputs and abundance control to produce cell-type-specific positive or negative secretory outputs remains incompletely defined.
  • No unified structural map of all effector interfaces on Rab27a
  • Identity of the E3 ligase controlling Rab27a turnover unknown
  • Determinants selecting which effector engages Rab27a in a given cell undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 4 GO:0098772 molecular function regulator activity 4
Localization
GO:0031410 cytoplasmic vesicle 4 GO:0005886 plasma membrane 3 GO:0005768 endosome 2 GO:0005829 cytosol 2
Pathway
R-HSA-168256 Immune System 4 R-HSA-9609507 Protein localization 4 R-HSA-5653656 Vesicle-mediated transport 3
Partners
EXPH5MLPHMYRIPSPIRE1SYTL2SYTL4TBC1D10AUNC13D
Complex memberships
Rab27a-MyRIP-myosin VIIa complexRab27a-melanophilin-myosin Va complexRab2a-Noc2-Rab27a complex

Evidence

Reading pass · 54 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Loss-of-function mutations in RAB27A cause Griscelli syndrome type 2, with RAB27A-deficient T cells showing reduced cytotoxicity and cytolytic granule exocytosis, establishing RAB27A as a key effector of cytotoxic granule exocytosis in immune homeostasis. Human genetics (homozygosity mapping, mutation identification), functional cytotoxicity and granule exocytosis assays in patient T cells Nature genetics High 10835631
2000 The ashen mouse mutation encodes Rab27a; Rab27a-deficient mice display defects in pigment granule transport in melanocytes and reduced platelet dense granules, establishing Rab27a as critical for organelle-specific protein trafficking in melanocytes and platelets. Positional cloning, BAC rescue, platelet function assays (bleeding time, dense granule counting) Proceedings of the National Academy of Sciences of the United States of America High 10859366
2001 Rab27a is required for the final secretory step (membrane docking) of lytic granules at the immunological synapse in cytotoxic T lymphocytes; ashen (Rab27a-null) CTLs show granule polarization but no membrane docking, while gunmetal CTLs (with underprenylated, cytosol-redistributed Rab27a) show partial polarization defects. CTL cytotoxicity assays, granzyme/hexosaminidase secretion assays, immunofluorescence and electron microscopy The Journal of cell biology High 11266472
2001 Rab27a decorates melanosomes and regulates their peripheral distribution; dominant-negative Rab27a mutants cause perinuclear melanosome clustering; Rab27a is necessary for recruitment of myosin Va to the melanosome, as myosin Va co-immunoprecipitates with Rab27a and is greatly reduced on melanosomes from Rab27a-deficient ashen melanocytes. Immunofluorescence, overexpression of dominant-negative mutants, co-immunoprecipitation from melanocyte extracts, comparison of wild-type vs. ashen melanocytes The Journal of cell biology High 11266470
2001 Re-expression of Rab27a in melanocytes from a Griscelli syndrome patient restored melanosome transport to dendrite tips, providing direct evidence that Rab27a is a key component of the vesicle transport machinery in melanocytes. Immunofluorescence, immunoelectron microscopy, functional rescue by Rab27a re-expression in patient-derived GS melanocytes The Journal of cell biology High 11266474
2002 Slac2-a/melanophilin is the molecular linker between GTP-Rab27A on the melanosome and myosin Va, forming a tripartite complex (Rab27A·Slac2-a·myosin Va) that regulates melanosome transport; the N-terminal SHD of Slac2-a specifically binds GTP-Rab27A/B, and the C-terminal half binds myosin Va globular tail. Deletion analysis, site-directed mutagenesis, co-immunoprecipitation from melanoma cells, in vitro binding assays The Journal of biological chemistry High 11856727
2002 A conserved N-terminal Rab27-binding domain (similar to Rab3a-binding domain of rabphilin-3) is shared by melanophilin and JFC1/Slp1; this domain binds Rab27a in a GTP-dependent manner, and overexpression causes perinuclear melanosome clustering, confirming functional interaction with Rab27a in melanocytes. Yeast two-hybrid, multiple binding assays, overexpression in melanocytes with melanosome distribution readout, Co-IP of melanophilin with Rab27a and myosin Va on melanosomes The Journal of biological chemistry High 11980908
2002 Melanophilin directly and simultaneously binds Rab27a (via N-terminal region) and myosin Va (via first C-terminal coiled-coil region), forming a ternary complex in the human melanocyte cell line HMV-II, bridging Rab27a on melanosomes to myosin Va on actin filaments. Cosedimentation assays with recombinant proteins, co-immunoprecipitation from HMV-II cells FEBS letters High 12062444
2002 Rab27a is an essential component of the melanosome receptor for myosin Va; binding requires the melanocyte-specific exon F of myosin Va; the interaction is GTP-Rab27a-dependent and indirect (requiring at least one additional bridging protein), as pure Rab27a does not bind myosin Va-coated beads directly. Pulldown assays with purified proteins and melanocyte lysates, exon-swap myosin Va constructs, GDP vs. GTPγS nucleotide conditions Molecular biology of the cell High 12006666
2002 Granuphilin interacts with the GTP form of Rab27a via its N-terminal zinc-finger domain and co-localizes with Rab27a on insulin granule membranes in pancreatic beta cells; overexpression of wild-type Rab27a or its GTPase-deficient mutant enhances high K+-induced insulin secretion, establishing Rab27a as a regulator of dense-core granule exocytosis in beta cells. Yeast two-hybrid, co-immunoprecipitation from MIN6 cells, immunofluorescence, immunoelectron microscopy, sucrose density gradient fractionation, insulin secretion assays Molecular and cellular biology High 11865063
2002 Slac2-c/MyRIP binds GTP-Rab27A/B via its N-terminal SHD, and also interacts with myosin Va and myosin VIIa; its C-terminal actin-binding domain co-localizes with actin at the cell periphery, suggesting a role in capturing Rab27-containing organelles in the actin-enriched cell cortex. In vitro binding assays, co-immunoprecipitation, cell expression/co-localization studies in PC12 cells and melanoma cells The Journal of biological chemistry Medium 12221080
2002 Rab27b can functionally substitute for Rab27a in melanocytes (rescuing ashen coat color and melanosome distribution), but Rab27b is not expressed in melanocytes or CTLs under normal conditions, explaining the cell-type-specific manifestation of Griscelli syndrome. Transgenic mouse rescue (ubiquitous Rab27a or Rab27b expression in ashen mice), transient expression in ashen melanocytes, organelle morphology in platelets The Journal of clinical investigation High 12122117
2002 Three Griscelli syndrome missense mutations in Rab27a (Ala152Pro, Leu130Pro, Trp73Gly) define critical functional residues: Ala152Pro and Leu130Pro dramatically reduce GTP/GDP binding by disrupting protein folding; Trp73Gly retains GTP binding and GTPase activity but abolishes effector (melanophilin) interaction and fails to rescue melanosome distribution or granule exocytosis, identifying Trp73 as essential for effector engagement. Biochemical nucleotide-binding assays, GTPase activity measurements, co-immunoprecipitation, melanosome distribution assays in melanocytes, CTL exocytosis assays Blood High 12446441
2002 Slp5 (synaptotagmin-like protein 5) is a novel Rab27A effector; its SHD preferentially binds GTP-bound Rab27A (not other Rabs tested) both in vitro and in intact cells, and the in vivo association is confirmed by immunoprecipitation from mouse liver. In vitro binding assays, transfection in COS-7 cells, co-immunoprecipitation from mouse liver Biochemical and biophysical research communications Medium 12051743
2003 Munc13-4, identified by affinity purification from platelets as a GTP-Rab27A-binding protein, directly binds GTP-Rab27A/B in vitro and enhances platelet dense core granule secretion; unprenylated active Rab27A inhibits secretion, and this is rescued by Munc13-4, establishing Munc13-4 as a Rab27 effector mediating dense granule secretion in platelets. Affinity purification from platelet lysates, in vitro binding assay with recombinant proteins, permeabilized platelet secretion assay The Journal of biological chemistry High 14699162
2003 Rab27a is expressed in a broad range of specialized secretory cells (exocrine, endocrine, ovarian, hematopoietic) as demonstrated by EGFP-Rab27a knock-in transgenic mice; the EGFP-Rab27a fusion protein is fully functional and rescues ashen defects, establishing a general role for Rab27a in regulated exocytosis. PAC-based EGFP-Rab27a transgenic mice, rescue of ashen phenotype, cell-type specific expression analysis Molecular biology of the cell High 14617806
2003 Rab27a (via its effector Slac2c/MyRIP) regulates insulin exocytosis in pancreatic beta cells; siRNA knockdown of Rab27a impairs secretagogue-stimulated insulin secretion; Slac2c/MyRIP associates with insulin granules via Rab27a, and its actin-binding domain is required for exocytosis, suggesting the complex mediates granule interaction with cortical actin. RNA interference (siRNA) in beta cells, insulin secretion assays, overexpression of domain mutants, immunolocalization Molecular biology of the cell High 14517322
2004 Slp2-a is the most abundant Rab27A-binding protein in melanocytes; siRNA knockdown of Slp2-a reduces peripheral melanosome number ('peripheral dilution') and alters melanocyte morphology from elongated to rounded; Slp2-a requires both phospholipid-binding and Rab27A-binding activities for melanosome distribution, but only phospholipid-binding for cell shape control. siRNA knockdown in melanocytes, rescue with siRNA-resistant Slp2-a and domain mutants, melanosome distribution quantification, morphology analysis Nature cell biology High 15543135
1995 Rab27 (then called Ram/Rab27) is deficiently geranylgeranylated in choroideremia cells because it preferentially depends on REP-1 (Rab escort protein-1) over REP-2 for prenylation; Rab27 accumulates unprenylated in choroideremia lymphoblasts and can be prenylated in vitro more efficiently by REP-1 than REP-2. Recombinant Rab geranylgeranyl transferase in vitro prenylation assay, purification of unprenylated cytosolic protein from choroideremia lymphoblasts, protein identification, immunohistochemistry The Journal of biological chemistry High 7592656
2006 Missense mutation Ala87Pro in Rab27a prevents formation of a stable Munc13-4/Rab27a complex in a mammalian two-hybrid system, demonstrating that this residue is critical for the Rab27a–Munc13-4 interaction required for granule exocytosis. Mammalian two-hybrid system, functional analysis of missense mutants Human mutation Medium 16278825
2006 EPI64, a TBC-domain protein, is identified as a GTPase-activating protein (GAP) specific for Rab27A; EPI64 induces melanosome aggregation in melanocytes and has in vitro Rab27A-GAP activity; mutations in its catalytic domain abolish this activity. Functional screen of 40 TBC proteins for melanosome aggregation in melanocytes, GTP-Rab27A trapping assay with SHD of Slac2-a, in vitro GAP activity assay, catalytic domain mutagenesis The Journal of biological chemistry High 16923811
2006 Rab3A and Rab27A cooperatively regulate docking of dense-core vesicles to the plasma membrane in PC12 cells; siRNA silencing of either Rab3A or Rab27A decreases the number of docked vesicles without altering kinetics of individual fusion events; simultaneous knockdown causes a greater decrease, demonstrating cooperative but independent roles. siRNA knockdown of Rab3A and Rab27A (individually and combined), total internal reflection fluorescence (TIRF) microscopy in single PC12 cells Journal of cell science High 16684812
2006 Rab27a is constitutively present in GTP-bound form in resting platelets due to constitutive GDP/GTP exchange activity; upon secretion stimulation, GTP hydrolysis is enhanced; GTP hydrolysis of Rab27 is not necessary to trigger secretion per se, as loading with non-hydrolyzable GppNHp does not block Ca2+-induced secretion. TLC analysis of nucleotides on immunoprecipitated Rab27, pulldown with GTP-Rab27-binding SHD domain, permeabilized platelet secretion assay with GppNHp The Journal of biological chemistry Medium 16880209
2007 Rab27a and Myrip form a ternary complex with Myosin VIIa on RPE melanosomes; disruption of any component (ashen Rab27a-deficient cells, shaker-1 MyoVIIa mutant, or Myrip siRNA knockdown) leads to increased melanosome motility, more frequent bursts of fast movement, and reversed directionality, suggesting the Rab27a-Myrip-MyoVIIa complex tethers melanosomes to actin toward the cell periphery. Co-immunoprecipitation, immunofluorescence/immunoelectron microscopy, live-cell imaging of RPE primary cultures, nocodazole and cytochalasin D treatments, ashen and shaker-1 mouse models, adenoviral shRNA knockdown Traffic (Copenhagen, Denmark) High 17451552
2007 Rab27a and its effector MyRIP are both present on mature Weibel-Palade bodies (WPBs) in endothelial cells; siRNA depletion of either Rab27a or MyRIP causes loss of peripheral WPB localization, increased basal and stimulated VWF secretion, and release of less multimerized VWF with shorter strings under flow, establishing a Rab27a/MyRIP complex that anchors WPBs to peripheral actin and limits/controls VWF release. siRNA depletion in primary endothelial cells, WPB localization imaging, VWF multimer analysis, flow chamber assay for VWF string length Blood High 19270261
2007 Rab27a is a key component of the secretory machinery for azurophilic granules in granulocytes; Rab27a and its effector JFC1/Slp1 co-localize on a minor subpopulation of MPO-containing granules; interference with the JFC1/Slp1-Rab27a complex impairs extracellular MPO secretion but not phagosomal MPO delivery. Rab27a-deficient mouse model, LPS-induced MPO secretion in vivo, cell fractionation, immunofluorescence, permeabilized neutrophil secretion assay, HL-60 siRNA knockdown The Biochemical journal High 17090228
2007 Rab27a interaction with its effector melanophilin (Mlph) is required for melanosome targeting and stability of Mlph on melanosomes; Mlph-Rab27a interaction is needed for melanosome transport to peripheral dendrites via recruitment of myosin Va (MyoVa); EB1 interaction with Mlph is non-essential for this process in cultured melanocytes. siRNA knockdown of Rab27a, MyoVa, EB1; Mlph point mutants (R35W blocking Rab27a binding); melanosome distribution quantification in cultured melanocytes Journal of cell science High 17698919
2007 EGFP-Rab27A on secretory granules in PC12 cells shows slow FRAP recovery (comparable to cargo protein ppANF), unlike EGFP-Rab3A which recovers rapidly, indicating Rab27A (but not Rab3A) does not rapidly exchange between granules and cytosol; both Rab3A and Rab27A preferentially associate with newly synthesized granules. FRAP (fluorescence recovery after photobleaching), co-localization with secretogranin II, live-cell imaging during stimulation Journal of cell science Medium 17311845
2008 Crystal structure of constitutively active Rab27B complexed with GTP and the effector domain of Slac2-a reveals intermolecular hydrogen bonds not observed in Rab3A/rabphilin complex; a Rab27A mutation disrupting one specific hydrogen bond dramatically reduces Slac2-a binding; transplanting four Rab27-specific residues into Rab3A confers Slac2-a binding ability, defining the structural basis for exclusive Rab27 subfamily specificity. Crystal structure determination, site-directed mutagenesis, in vitro binding assays Structure (London, England : 1993) High 18940604
2008 The G43S switch I region mutation of Rab27A (found in Griscelli syndrome) causes perinuclear melanosome localization in normal melanocytes and fails to restore peripheral melanosome distribution in GS melanocytes; co-immunoprecipitation shows G43S fails to interact with melanophilin, establishing the switch I region as required for Rab27A-effector interaction. Laser scanning confocal microscopy, co-immunoprecipitation, expression in normal and GS patient melanocytes Molecular genetics and metabolism Medium 18397837
2008 Rab27a-null (ashen) pancreatic beta cells display a kinetic defect in refilling of the immediately releasable pool (IRP) and readily releasable pool (RRP) of insulin granules following depolarization; GTP/GDP cycling of Rab27A is essential for IRP generation; these defects are rescued by cAMP/PKA activation acting downstream of or independently of Rab27a. Membrane capacitance measurements in ashen vs. wild-type beta cells, pharmacological dissection with cAMP/PKA inhibitors, comparison with Rab3a-null cells The Journal of physiology High 18801842
2009 Rab27a and Rab27b control different steps of exosome secretion in HeLa cells: Rab27a silencing causes increased MVE size; Rab27b silencing redistributes MVEs to the perinuclear region; both isoforms mediate MVE docking at the plasma membrane. Effectors Slp4 (SYTL4) and Slac2b (EXPH5) phenocopy Rab27a and Rab27b silencing respectively. RNAi screen of Rab GTPases for exosome secretion, electron microscopy of MVE morphology/localization, effector siRNA knockdowns Nature cell biology High 19966785
2009 Both Rab27a and Rab27b regulate azurophilic granule exocytosis in neutrophils by independent mechanisms; TIRF microscopy shows reduced number of azurophilic granules near the plasma membrane in Rab27a-deficient, Rab27b-KO, and double-KO neutrophils; Rab27-deficient neutrophils also show impaired NADPH oxidase activation at the plasma membrane but intact phagosomal ROS production. Rab27a-ashen, Rab27b-KO, and double-KO mouse neutrophils; TIRF microscopy, secretion assays, NADPH oxidase activity measurements Traffic (Copenhagen, Denmark) High 20028487
2009 Different NK cell-activating receptor signals preferentially recruit either Rab27a or Munc13-4 to perforin-containing lytic granules; LFA-1, NKG2D, and 2B4 receptor engagement induces Rab27a co-localization with perforin but not Munc13-4, whereas CD16 induces Munc13-4 co-localization; Munc13-4 co-localization with perforin is Rab27a-dependent, placing Rab27a upstream of Munc13-4 in lytic granule maturation. NK cell degranulation assays (CD107a expression), immunofluorescence confocal imaging of receptor-specific stimulation, analysis of Rab27a-deficient patient NK cells Blood High 19704116
2010 Two GS-2 RAB27A missense mutations, K22R and I44T, both abolish Slac2-a/melanophilin binding but differ mechanistically: K22R lacks GTP binding and shows cytosolic localization; I44T retains intrinsic GTPase activity and melanosomal localization but cannot recruit melanophilin; the two mutations differentially affect binding to Slp2-a, Slp4-a/granuphilin-a, and Munc13-4, mapping distinct binding interfaces on Rab27a for different effectors. Biochemical GTPase assays, pulldown/binding assays with recombinant effectors, immunofluorescence in melanocytes Pigment cell & melanoma research High 20370853
2010 Rab27a negatively regulates complement-mediated phagocytosis by prolonging the actin-coating stage around phagosomes; Rab27a knockdown in HL-60 macrophages enhances phagocytosis and accelerates F-actin remodeling; this requires GTP-bound Rab27a (Q78L rescues, T23N does not); Coronin 1A accumulation is increased in Rab27a knockdown cells, suggesting Rab27a suppresses Coronin 1A to prolong actin coating. shRNA knockdown and rescue in HL-60 cells, phagocytosis assays with C3bi-opsonized zymosan, microscopic F-actin dynamics analysis, GTPase mutants The Journal of biological chemistry Medium 21169636
2010 Rab27a is required for human cytomegalovirus (HCMV) assembly; HCMV infection increases Rab27a expression and recruits it to viral envelopes at the assembly site; Rab27a knockdown and Rab27a-deficient ashen melanocytes both reduce CMV production. siRNA knockdown, Rab27a-deficient ashen melanocytes, immunogold labeling of viral envelopes, virus titer assays PloS one Medium 21170347
2011 Rab27a and Rab27b regulate stimulation-dependent RANKL release from secretory lysosomes in osteoblastic cells; siRNA suppression of either Rab27a or Rab27b markedly reduces RANKL release; effectors Slp4-a, Slp5, and Munc13-4 coordinate Rab27a/b activity; Jinx mice (lacking Munc13-4) show increased bone volume due to low resorptive activity, confirming in vivo relevance. siRNA knockdown in osteoblastic cells, RANKL secretion assays, effector knockdown, in vivo bone phenotyping of Munc13-4-deficient (Jinx) mice Journal of bone and mineral research High 20939018
2012 In Weibel-Palade body exocytosis, Slp4-a (granuphilin) is a positive regulator and MyRIP is a negative regulator; both effects are mediated by Rab27A; Rab27A cycles between WPBs and a cytosolic pool; the probability of WPB release is determined by the fractional occupancy of WPB-Rab27A by Slp4-a vs. MyRIP rather than absolute amounts. siRNA knockdown of Rab27A, Slp4-a, MyRIP, Rab3B, Rab3D; EGFP-Slp4-a and EGFP-MyRIP overexpression; live imaging to track WPB exocytosis Blood High 22898601
2012 Slp2-a (Rab27 effector) is required for targeting podocalyxin to the apical membrane of MDCK II cells in a Rab27A-dependent manner; Slp2-a knockdown activates ezrin and ERK1/2, reducing claudin-2 expression; Slp2-a expression increases during cell polarization and localizes to the apical membrane. siRNA knockdown in MDCK II cells, immunofluorescence, western blot for ezrin and ERK activation, claudin-2 expression analysis Molecular biology of the cell Medium 22767581
2013 Rab27a plays an inhibitory role in mast cell degranulation through the Mlph/MyoVa pathway by regulating cortical F-actin stability; ashen BMMCs have abnormal cortical F-actin and hypersecretion; actin disassembly increases wild-type BMMC secretion to ashen levels; Rab27b/Munc13-4 regulates a positive exocytic step. This reveals opposing roles for Rab27a/Mlph/MyoVa and Rab27b/Munc13-4 in mast cells. BMMC from Rab27a-deficient, Rab27b-KO, Mlph-deficient (leaden), MyoVa-deficient (dilute), Munc13-4-deficient (jinx) mice; degranulation assays; F-actin staining; cytochalasin D treatment The FEBS journal High 23281710
2013 MADD/DENN/Rab3GEP functions as a guanine nucleotide exchange factor (GEF) for Rab27 in rat parotid acinar cells; antibody against MADD inhibits isoproterenol-induced amylase release and reduces GTP-Rab27 levels in permeabilized acinar cells. RT-PCR for DENN family expression, antibody inhibition in permeabilized parotid acinar cells, GTP-Rab27 measurement by pulldown Archives of biochemistry and biophysics Medium 23702376
2014 RAB27A mutations at residues R141, Y159, or S163 disrupt Rab27a-Munc13-4 interaction without impairing Rab27a-melanophilin interaction, causing GS-2 with immunodeficiency but normal pigmentation; this maps a distinct binding site for Munc13-4 on Rab27a separate from the melanophilin-binding interface. RAB27A sequencing in GS patients, functional binding assays for effector interactions in patient-derived cells The Journal of allergy and clinical immunology High 25312756
2014 GTP/GDP nucleotide cycling of Rab27A (achieved by EPI64A GAP overexpression) is essential for generation of the immediately releasable pool (IRP) and regulation of the readily releasable pool (RRP) of insulin granules in beta cells; Rab3 cycling controls kinetically rapid RRP filling; Rab3 and Rab27A show both distinct and overlapping roles in exocytosis. Rab3GAP and EPI64A overexpression in wild-type and ashen beta cells, membrane capacitance measurements Traffic (Copenhagen, Denmark) High 24909540
2015 Rab27a controls trafficking of PI4KIIα-positive late endosomes to the plasma membrane of CD4+ T cells, thereby promoting high levels of PM phosphatidylinositol 4-phosphate and localized PI(4,5)P2 production; this controls Pr55(Gag) membrane association and HIV-1 assembly. Effectors Slp2a, Slp3, and Slac2b are required for Pr55(Gag) PM association, and Slp2a cooperates with Rab27a in PI4KIIα recruitment. Rab27a siRNA knockdown in CD4+ T cells and macrophages, live imaging of PI4KIIα trafficking, PI(4,5)P2 measurement, Rab27a effector screen, HIV-1 assembly assay The Journal of cell biology High 25940347
2016 Heterozygous RAB27A mutation A87P decreases NK cell cytolytic activity and degranulation, reduces binding of Rab27A to Munc13-4 (proximity ligation assay), and delays granzyme B polarization to the immunologic synapse; this partial dominant-negative effect contributes to HLH pathogenesis. Lentiviral expression of mutant Rab27A in NK-92 cells, degranulation (CD107a), cytotoxicity assays, confocal microscopy for granzyme B localization, proximity ligation assay for Rab27A-Munc13-4 interaction Journal of immunology (Baltimore, Md. : 1950) Medium 26880764
2016 Rab2a and Rab27a simultaneously bind the dual effector Noc2 in a GTP-dependent manner (Rab2a binding requires prior Rab27a binding); the ternary Rab2a-Noc2-Rab27a complex localizes on perinuclear immature insulin granules while the binary Noc2-Rab27a complex is on peripheral mature granules; Noc2 mutants defective in either Rab binding fail to promote glucose-stimulated insulin secretion; knockdown of Rab2a or Noc2 (but not Rab27a) impairs proinsulin-to-insulin processing, establishing Rab27a's role in the late exocytic steps downstream of granule maturation. GTP-dependent co-immunoprecipitation, immunofluorescence in pancreatic beta cells, Noc2 mutant overexpression, siRNA knockdown of each component, insulin secretion assays, proinsulin processing assays Journal of cell science High 27927751
2019 KIBRA (kidney and brain protein) stabilizes Rab27a by preventing its ubiquitination and proteasomal degradation; KIBRA knockdown reduces Rab27a protein levels, increases MVB size and number, and decreases exosome secretion; KIBRA overexpression increases exosome secretion; KIBRA knockout mouse brains show significantly decreased Rab27a. siRNA knockdown and overexpression in neuronal and podocyte cell lines, co-immunoprecipitation, KIBRA-KO mouse brain proteomics, ubiquitination assay, electron microscopy of MVBs Nature communications High 30967557
2019 RAB27A loss in melanoma cells inhibits 3D spheroid invasion and spontaneous metastasis in vivo; reduced invasion is rescued by RAB27A-replete but not RAB27A-knockdown exosomes; RAB27A loss does not alter exosome number but changes exosome size and protein composition, establishing RAB27A as promoting biogenesis of a distinct pro-invasive exosome population. RAB27A knockdown in melanoma cell lines, 3D spheroid invasion assays, in vivo spontaneous metastasis, exosome rescue experiments, exosome size/proteome analysis International journal of cancer Medium 30556600
2020 SPIRE-type actin nucleators (predominantly SPIRE1) are Rab27a effectors that co-operate with formin-1 to generate actin tracks required for myosin-Va-dependent long-range melanosome transport in melanocytes; Rab27a thus coordinates both motor (myosin-Va via melanophilin) and actin track assembly (via SPIRE1) at the melanosome membrane. Identification of SPIRE1 as Rab27a effector, co-localization, genetic epistasis (knockout/knockdown of SPIRE1, formin-1, melanophilin), live imaging of melanosome transport Nature communications High 32661310
2018 IRF-1 (interferon regulatory factor 1) transcriptionally regulates Rab27a expression; IRF-1 binding motifs in the Rab27a promoter were confirmed by chromatin immunoprecipitation, EMSA, and luciferase assay; IRF-1 induction or ischemia-reperfusion increases Rab27a expression and extracellular vesicle secretion; Rab27a silencing decreases EV secretion and liver IR injury. ChIP, EMSA, luciferase reporter assay, IRF-1 overexpression/siRNA, Rab27a siRNA knockdown, EV quantification, liver IR model Hepatology (Baltimore, Md. : 1950) High 29059701
2020 GS-2 patient with novel Val143Ala RAB27A mutation shows impaired RAB27A-SLP2-A and RAB27A-MUNC13-4 interactions but intact RAB27A-melanophilin interaction; the patient has HLH without albinism, providing a separation-of-function map of effector binding sites on RAB27A. RAB27A mutation identification, cell-line binding assays for multiple effectors in relevant cell types Frontiers in immunology Medium 33362801
2006 Rab27a regulates epithelial sodium channel (ENaC) activity in a GTP-dependent manner; GTP-locked Rab27a Q78L inhibits amiloride-sensitive currents, while GDP-locked T23N has no effect; SLP-5 and Munc13-4 compete with ENaC for Rab27a binding, relieving Rab27a-mediated ENaC inhibition. Electrophysiology (ENaC current measurements), competitive co-immunoprecipitation assays, expression of GTPase mutants and effector domain constructs in HT-29 cells Biochemical and biophysical research communications Medium 16630545
2005 JFC1/Slp1, a Rab27a-binding protein, is phosphorylated by Akt at serine 241; phosphorylation causes JFC1 dissociation from the membrane and redistribution to the cytosol but does not alter JFC1-Rab27a binding affinity; phosphorylation by Akt is reduced when JFC1 is bound to Rab27a, and the JFC1-Rab27a interaction occurs near the plasma membrane. In vitro Akt phosphorylation assay, microcapillary HPLC-MS/MS identification of phosphorylation sites, mutagenesis, co-immunoprecipitation, subcellular fractionation Traffic (Copenhagen, Denmark) Medium 15998322

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Rab27a and Rab27b control different steps of the exosome secretion pathway. Nature cell biology 2160 19966785
2000 Mutations in RAB27A cause Griscelli syndrome associated with haemophagocytic syndrome. Nature genetics 715 10835631
2000 A mutation in Rab27a causes the vesicle transport defects observed in ashen mice. Proceedings of the National Academy of Sciences of the United States of America 340 10859366
2001 Rab27a is required for regulated secretion in cytotoxic T lymphocytes. The Journal of cell biology 326 11266472
2002 Slac2-a/melanophilin, the missing link between Rab27 and myosin Va: implications of a tripartite protein complex for melanosome transport. The Journal of biological chemistry 300 11856727
2001 Rab27a regulates the peripheral distribution of melanosomes in melanocytes. The Journal of cell biology 280 11266470
2002 A family of Rab27-binding proteins. Melanophilin links Rab27a and myosin Va function in melanosome transport. The Journal of biological chemistry 269 11980908
2014 Cellular disposal of miR23b by RAB27-dependent exosome release is linked to acquisition of metastatic properties. Cancer research 246 25261234
2006 Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A. Human mutation 225 16278825
2013 Rab27 effectors, pleiotropic regulators in secretory pathways. Traffic (Copenhagen, Denmark) 196 23678941
1995 Deficient geranylgeranylation of Ram/Rab27 in choroideremia. The Journal of biological chemistry 196 7592656
2002 The Rab27a/granuphilin complex regulates the exocytosis of insulin-containing dense-core granules. Molecular and cellular biology 194 11865063
2019 KIBRA controls exosome secretion via inhibiting the proteasomal degradation of Rab27a. Nature communications 193 30967557
2005 Versatile role of Rab27 in membrane trafficking: focus on the Rab27 effector families. Journal of biochemistry 189 15713878
2001 Rab27a: A key to melanosome transport in human melanocytes. The Journal of cell biology 177 11266474
2003 Munc13-4 is a GTP-Rab27-binding protein regulating dense core granule secretion in platelets. The Journal of biological chemistry 163 14699162
2006 Rab3A and Rab27A cooperatively regulate the docking step of dense-core vesicle exocytosis in PC12 cells. Journal of cell science 160 16684812
2002 Functional redundancy of Rab27 proteins and the pathogenesis of Griscelli syndrome. The Journal of clinical investigation 142 12122117
2002 Rab27a is an essential component of melanosome receptor for myosin Va. Molecular biology of the cell 141 12006666
2003 A general role for Rab27a in secretory cells. Molecular biology of the cell 139 14617806
2002 Slac2-c (synaptotagmin-like protein homologue lacking C2 domains-c), a novel linker protein that interacts with Rab27, myosin Va/VIIa, and actin. The Journal of biological chemistry 137 12221080
2003 Involvement of the Rab27 binding protein Slac2c/MyRIP in insulin exocytosis. Molecular biology of the cell 135 14517322
2004 Rab27A-binding protein Slp2-a is required for peripheral melanosome distribution and elongated cell shape in melanocytes. Nature cell biology 128 15543135
2002 Melanophilin directly links Rab27a and myosin Va through its distinct coiled-coil regions. FEBS letters 124 12062444
2018 Circ-BPTF promotes bladder cancer progression and recurrence through the miR-31-5p/RAB27A axis. Aging 107 30103209
1997 Molecular cloning and characterization of rab27a and rab27b, novel human rab proteins shared by melanocytes and platelets. Biochemical and molecular medicine 105 9066979
2008 Enhanced expression of Rab27A gene by breast cancer cells promoting invasiveness and the metastasis potential by secretion of insulin-like growth factor-II. Molecular cancer research : MCR 101 18337447
2003 The roles of Rab27 and its effectors in the regulated secretory pathways. Cell structure and function 96 14745138
2019 RAB27A promotes melanoma cell invasion and metastasis via regulation of pro-invasive exosomes. International journal of cancer 91 30556600
2009 Rab27a and MyRIP regulate the amount and multimeric state of VWF released from endothelial cells. Blood 88 19270261
2009 Rab27a and Rab27b regulate neutrophil azurophilic granule exocytosis and NADPH oxidase activity by independent mechanisms. Traffic (Copenhagen, Denmark) 88 20028487
2017 Rab27-Dependent Exosome Production Inhibits Chronic Inflammation and Enables Acute Responses to Inflammatory Stimuli. Journal of immunology (Baltimore, Md. : 1950) 85 28978688
2009 Different NK cell-activating receptors preferentially recruit Rab27a or Munc13-4 to perforin-containing granules for cytotoxicity. Blood 85 19704116
2007 Rab27a and MyoVa are the primary Mlph interactors regulating melanosome transport in melanocytes. Journal of cell science 85 17698919
2012 The interplay between the Rab27A effectors Slp4-a and MyRIP controls hormone-evoked Weibel-Palade body exocytosis. Blood 83 22898601
2007 The ternary Rab27a-Myrip-Myosin VIIa complex regulates melanosome motility in the retinal pigment epithelium. Traffic (Copenhagen, Denmark) 79 17451552
2016 A Heterozygous RAB27A Mutation Associated with Delayed Cytolytic Granule Polarization and Hemophagocytic Lymphohistiocytosis. Journal of immunology (Baltimore, Md. : 1950) 75 26880764
2006 Identification of EPI64 as a GTPase-activating protein specific for Rab27A. The Journal of biological chemistry 75 16923811
2006 Rab7 and Rab27a control two motor protein activities involved in melanosomal transport. Pigment cell research 74 16965270
2007 Rab27a is a key component of the secretory machinery of azurophilic granules in granulocytes. The Biochemical journal 73 17090228
2012 Differential expression of Rab27A/B correlates with clinical outcome in hepatocellular carcinoma. World journal of gastroenterology 72 22553406
2018 Functional implications of Rab27 GTPases in Cancer. Cell communication and signaling : CCS 69 30081925
2002 Biochemical and functional characterization of Rab27a mutations occurring in Griscelli syndrome patients. Blood 69 12446441
2015 Rab27a controls HIV-1 assembly by regulating plasma membrane levels of phosphatidylinositol 4,5-bisphosphate. The Journal of cell biology 68 25940347
2002 Synaptotagmin-like protein 5: a novel Rab27A effector with C-terminal tandem C2 domains. Biochemical and biophysical research communications 68 12051743
2006 Rab27 and its effectors in secretory granule exocytosis: a novel docking machinery composed of a Rab27.effector complex. Biochemical Society transactions 64 17052176
2013 Distinct and opposing roles for Rab27a/Mlph/MyoVa and Rab27b/Munc13-4 in mast cell secretion. The FEBS journal 62 23281710
2015 Rab27A regulates transport of cell surface receptors modulating multinucleation and lysosome-related organelles in osteoclasts. Scientific reports 60 25882854
2012 Monitoring the Rab27 associated exosome pathway using nanoparticle tracking analysis. Experimental cell research 60 23092844
2008 Structural basis for the exclusive specificity of Slac2-a/melanophilin for the Rab27 GTPases. Structure (London, England : 1993) 60 18940604
2007 Differential dynamics of Rab3A and Rab27A on secretory granules. Journal of cell science 56 17311845
2018 Interferon regulatory factor 1-Rab27a regulated extracellular vesicles promote liver ischemia/reperfusion injury. Hepatology (Baltimore, Md.) 54 29059701
2010 Rab27a is required for human cytomegalovirus assembly. PloS one 53 21170347
2007 Physiological roles of Rab27 effectors in regulated exocytosis. Endocrine journal 53 17664848
2006 Constitutive GDP/GTP exchange and secretion-dependent GTP hydrolysis activity for Rab27 in platelets. The Journal of biological chemistry 49 16880209
2008 Rab27a regulates exocytosis of tertiary and specific granules in human neutrophils. Journal of immunology (Baltimore, Md. : 1950) 48 18768832
2020 Rab27a co-ordinates actin-dependent transport by controlling organelle-associated motors and track assembly proteins. Nature communications 46 32661310
2015 Upregulation of miR-582-5p inhibits cell proliferation, cell cycle progression and invasion by targeting Rab27a in human colorectal carcinoma. Cancer gene therapy 45 26384136
2014 Patients with Griscelli syndrome and normal pigmentation identify RAB27A mutations that selectively disrupt MUNC13-4 binding. The Journal of allergy and clinical immunology 42 25312756
2021 RAB27A-dependent release of exosomes by liver cancer stem cells induces Nanog expression in their differentiated progenies and confers regorafenib resistance. Journal of gastroenterology and hepatology 41 34258777
2008 Kinetics of Rab27a-dependent actions on vesicle docking and priming in pancreatic beta-cells. The Journal of physiology 41 18801842
2005 Analysis of the role of Rab27 effector Slp4-a/Granuphilin-a in dense-core vesicle exocytosis. Methods in enzymology 39 16473610
1999 Cloning, mapping and characterization of the human RAB27A gene. Gene 39 10571040
2005 The Rab27a-binding protein, JFC1, regulates androgen-dependent secretion of prostate-specific antigen and prostatic-specific acid phosphatase. The Biochemical journal 38 16004602
2013 Regulation of vesicular trafficking and leukocyte function by Rab27 GTPases and their effectors. Journal of leukocyte biology 36 23378593
2012 Rab27 effector Slp2-a transports the apical signaling molecule podocalyxin to the apical surface of MDCK II cells and regulates claudin-2 expression. Molecular biology of the cell 35 22767581
2017 Effects of Rab27A and Rab27B on Invasion, Proliferation, Apoptosis, and Chemoresistance in Human Pancreatic Cancer Cells. Pancreas 34 28902788
2014 Distinct actions of Rab3 and Rab27 GTPases on late stages of exocytosis of insulin. Traffic (Copenhagen, Denmark) 34 24909540
2015 Supporting Role for GTPase Rab27a in Hepatitis C Virus RNA Replication through a Novel miR-122-Mediated Effect. PLoS pathogens 33 26305877
2021 In vivo Roles of Rab27 and Its Effectors in Exocytosis. Cell structure and function 32 34483204
2010 Rab27a negatively regulates phagocytosis by prolongation of the actin-coating stage around phagosomes. The Journal of biological chemistry 32 21169636
2005 Identification and biochemical analysis of Slac2-c/MyRIP as a Rab27A-, myosin Va/VIIa-, and actin-binding protein. Methods in enzymology 32 16473609
2017 RAB27A, RAB27B and VPS36 are downregulated in advanced prostate cancer and show functional relevance in prostate cancer cells. International journal of oncology 30 28197629
2013 Effects of Rab27a on proliferation, invasion, and anti-apoptosis in human glioma cell. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 30 23553027
2011 Rab27a and Rab27b are involved in stimulation-dependent RANKL release from secretory lysosomes in osteoblastic cells. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 30 20939018
2017 Rab27A overexpression promotes bladder cancer proliferation and chemoresistance through regulation of NF-κB signaling. Oncotarget 29 29088864
2016 Imbalanced Rab3D versus Rab27 increases cathepsin S secretion from lacrimal acini in a mouse model of Sjögren's Syndrome. American journal of physiology. Cell physiology 29 27076615
2008 A novel missense mutation (G43S) in the switch I region of Rab27A causing Griscelli syndrome. Molecular genetics and metabolism 29 18397837
2014 Analysis of microRNA-203 function in CREB/MITF/RAB27a pathway: comparison between canine and human melanoma cells. Veterinary and comparative oncology 28 25280339
2013 MADD/DENN/Rab3GEP functions as a guanine nucleotide exchange factor for Rab27 during granule exocytosis of rat parotid acinar cells. Archives of biochemistry and biophysics 27 23702376
2013 An essential role for Rab27a GTPase in eosinophil exocytosis. Journal of leukocyte biology 27 23986549
2005 Rab27a: a new face in beta cell metabolism-secretion coupling. The Journal of clinical investigation 26 15690078
2020 Rab27A promotes cellular apoptosis and ROS production by regulating the miRNA-124-3p/STAT3/RelA signalling pathway in ulcerative colitis. Journal of cellular and molecular medicine 25 32815642
2016 Rab3A, Rab27A, and Rab35 regulate different events during mouse oocyte meiotic maturation and activation. Histochemistry and cell biology 25 26791531
2023 Rab27a-mediated extracellular vesicle secretion contributes to osteogenesis in periodontal ligament-bone niche communication. Scientific reports 24 37231020
2022 Necroptosis is associated with Rab27-independent expulsion of extracellular vesicles containing RIPK3 and MLKL. Journal of extracellular vesicles 24 36063142
2020 Griscelli Syndrome Type 2 Sine Albinism: Unraveling Differential RAB27A Effector Engagement. Frontiers in immunology 24 33362801
2016 Rab27a regulates GM-CSF-dependent priming of neutrophil exocytosis. Journal of leukocyte biology 24 27733578
2016 Rab2a and Rab27a cooperatively regulate the transition from granule maturation to exocytosis through the dual effector Noc2. Journal of cell science 24 27927751
2021 miR-4454 Promotes Hepatic Carcinoma Progression by Targeting Vps4A and Rab27A. Oxidative medicine and cellular longevity 23 34777698
2014 A role for Rab27 in neutrophil chemotaxis and lung recruitment. BMC cell biology 23 25359237
2005 Akt regulates the subcellular localization of the Rab27a-binding protein JFC1 by phosphorylation. Traffic (Copenhagen, Denmark) 23 15998322
2021 MiR-186-5p suppresses cell migration, invasion, and epithelial mesenchymal transition in bladder cancer by targeting RAB27A/B. Environmental toxicology 22 34291859
2020 Rab27a plays a dual role in metastatic propensity of pancreatic cancer. Scientific reports 22 32355248
2010 Functional characterization of two RAB27A missense mutations found in Griscelli syndrome type 2. Pigment cell & melanoma research 22 20370853
2021 Platelet-rich plasma promotes MSCs exosomes paracrine to repair acute kidney injury via AKT/Rab27 pathway. American journal of translational research 21 33841669
2022 PRR34-AS1 promotes exosome secretion of VEGF and TGF-β via recruiting DDX3X to stabilize Rab27a mRNA in hepatocellular carcinoma. Journal of translational medicine 20 36303180
2018 Rab27a Regulates Human Perivascular Adipose Progenitor Cell Differentiation. Cardiovascular drugs and therapy 20 30105417
2006 Rab27a regulates epithelial sodium channel (ENaC) activity through synaptotagmin-like protein (SLP-5) and Munc13-4 effector mechanism. Biochemical and biophysical research communications 20 16630545
2002 Rapid degradation of dominant-negative Rab27 proteins in vivo precludes their use in transgenic mouse models. BMC cell biology 20 12401133

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