Affinage

RAB27A

Ras-related protein Rab-27A · UniProt P51159

Length
221 aa
Mass
24.9 kDa
Annotated
2026-04-28
100 papers in source corpus 28 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAB27A is a small GTPase that functions as a master organizer of regulated exocytosis across diverse secretory cell types, coordinating the peripheral capture, actin-based transport, docking, and fusion of lysosome-related organelles and secretory granules at the plasma membrane. In melanocytes, GTP-bound RAB27A on mature melanosomes recruits melanophilin/Slac2-a, which bridges to myosin Va for actin-dependent transport, and independently recruits SPIRE1 to nucleate the actin tracks themselves (PMID:11856727, PMID:32661310); its GTPase activity is required for correct melanosome targeting rather than transport per se (PMID:24584932). In cytotoxic lymphocytes, RAB27A engages Munc13-4 through a structurally separable binding interface to drive lytic granule docking and exocytosis, and mutations that selectively disrupt this interaction cause hemophagocytic lymphohistiocytosis without albinism, while broader loss-of-function mutations cause Griscelli syndrome type 2 (PMID:11266473, PMID:25312756). RAB27A also controls multivesicular endosome docking and exosome release, Weibel-Palade body anchoring in endothelial cells, insulin granule priming in β-cells, and NADPH oxidase delivery to phagosomes in dendritic cells, with its nucleotide state regulated by the GEF MADD/DENN and its protein stability maintained by KIBRA-mediated protection from ubiquitin-proteasomal degradation (PMID:19966785, PMID:19270261, PMID:24909540, PMID:17351642, PMID:23702376, PMID:30967557).

Mechanistic history

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

    Establishing that RAB27A has a uniquely stringent requirement for REP-1-mediated geranylgeranylation resolved why this particular Rab is unprenylated in choroideremia, linking its lipid modification to a specific disease context.

    Evidence In vitro prenylation assays with purified Rab geranylgeranyl transferase, REP-1, and REP-2 using choroideremia lymphoblasts

    PMID:7592656

    Open questions at the time
    • The functional consequence of reduced RAB27A prenylation in choroideremia retinal cells was not tested
    • No GAP or GEF was identified at this stage
  2. 2001 High

    Demonstrating that RAB27A loss abolishes lytic granule exocytosis in CTLs and NK cells while sparing constitutive secretion established RAB27A as a dedicated regulator of regulated exocytosis in immune cells, not a general trafficking factor.

    Evidence Ashen (Rab27a-null) mouse CTLs and NK cells; cytotoxicity assays, anti-CD3-stimulated granule secretion, immunolocalization with granzyme B

    PMID:11266473

    Open questions at the time
    • The downstream effector mediating granule docking/fusion in lymphocytes was unknown
    • Whether Rab27b could compensate in immune cells was untested
  3. 2002 High

    Identification of melanophilin/Slac2-a as the bridging adaptor that simultaneously binds GTP-RAB27A and myosin Va solved the long-standing question of how melanosomes are captured onto actin filaments, completing the tripartite transport complex model.

    Evidence Yeast two-hybrid, GST pulldowns, reciprocal co-IP from melanoma/melanocyte lysates, domain deletion/mutagenesis, dominant-negative overexpression phenotype

    PMID:11856727 PMID:11980908 PMID:12006666

    Open questions at the time
    • How RAB27A itself is targeted to melanosomes was unclear
    • The source of actin tracks for myosin Va was unresolved
    • Structural basis of Rab27-specific effector recognition was not yet available
  4. 2002 High

    Structure–function analysis of Griscelli syndrome mutations showed that Trp73 is critical for effector binding while other mutations (A152P, L130P) disrupt nucleotide binding, separating the effector-interaction and folding/nucleotide-binding defects underlying disease.

    Evidence Site-directed mutagenesis, GTP/GDP binding assays, co-IP with melanophilin, melanosome distribution and granule exocytosis assays

    PMID:12446441

    Open questions at the time
    • Whether different mutations selectively affect specific effectors (e.g., Munc13-4 vs. melanophilin) was not dissected
    • Clinical genotype–phenotype correlation was limited
  5. 2003 High

    Discovery of Munc13-4 as a direct GTP-RAB27A effector in platelets and MyRIP/Slac2c as an effector linking RAB27A to cortical actin in β-cells established that RAB27A engages cell-type-specific effectors to control secretion of diverse cargo.

    Evidence Affinity purification from platelets, in vitro binding, permeabilized platelet secretion rescue (Munc13-4); RNAi and domain mutagenesis with insulin secretion assays (MyRIP)

    PMID:14517322 PMID:14699162

    Open questions at the time
    • How Munc13-4 promotes fusion downstream of Rab27a was mechanistically unresolved
    • The full repertoire of Rab27a effectors across tissues was incomplete
  6. 2006 High

    Biochemical measurement of Rab27 nucleotide state in resting platelets showed it is predominantly GTP-loaded at steady state, and that GTP hydrolysis is not required for secretion itself, redefining the nucleotide cycle as important for localization/recycling rather than directly triggering fusion.

    Evidence TLC nucleotide analysis from immunoprecipitated Rab27; GppNHp loading in permeabilized platelets with Ca²⁺-triggered secretion

    PMID:16880209

    Open questions at the time
    • The specific GAP responsible for Rab27 inactivation in platelets was not identified
    • Whether this nucleotide cycle model applies to other Rab27a-dependent organelles was untested
  7. 2007 High

    Showing that Rab27a controls phagosomal pH by regulating NOX2-containing organelle recruitment in dendritic cells extended RAB27A function beyond exocytosis into innate immune antigen processing, explaining defective cross-presentation in Griscelli syndrome.

    Evidence Ashen mouse DCs; phagosomal pH measurements, NOX2 recruitment assays, cross-presentation functional assays

    PMID:17351642

    Open questions at the time
    • The specific effector mediating NOX2-containing organelle recruitment was not identified
    • Whether this pathway is relevant in human DCs was not shown
  8. 2008 High

    The crystal structure of GTP-Rab27B with the Slac2-a effector domain revealed the molecular determinants of exclusive Rab27 subfamily specificity, explaining why closely related Rab3 cannot substitute.

    Evidence X-ray crystallography of Rab27B·GTP·Slac2-a complex; mutagenesis transplanting four Rab27 residues into Rab3A conferred Slac2-a binding

    PMID:18940604

    Open questions at the time
    • Structures of Rab27a with other effectors (Munc13-4, MyRIP) were not determined
    • How the same Rab27 surface accommodates structurally diverse effectors was unresolved
  9. 2009 High

    Demonstrating that Rab27a and Rab27b control distinct steps of exosome biogenesis (MVE docking vs. perinuclear positioning) through specific effectors (Slp4 and Slac2b) established RAB27A as a central regulator of exosome secretion.

    Evidence Systematic RNAi screen in HeLa cells; siRNA of Rab27a, Rab27b, Slp4, Slac2b; exosome quantification; electron microscopy of MVE morphology

    PMID:19966785

    Open questions at the time
    • The fusion machinery downstream of Rab27a at the MVE–plasma membrane interface was unknown
    • Whether these roles are conserved across cell types was not established
  10. 2009 High

    Discovery that Rab27a and MyRIP restrain Weibel-Palade body release in endothelial cells by anchoring them to peripheral actin revealed an inhibitory (tethering) function complementing its exocytic role, showing RAB27A can both promote and restrain secretion depending on context.

    Evidence siRNA depletion of Rab27a and MyRIP in primary endothelial cells; VWF secretion and string length measurement under flow

    PMID:19270261

    Open questions at the time
    • The signal that releases Rab27a-mediated WPB tethering upon stimulation was not defined
    • Whether other Rab27a effectors participate in WPB exocytosis was untested
  11. 2013 Medium

    Identification of MADD/DENN as a GEF for Rab27 provided the first upstream activator, explaining how Rab27a is loaded with GTP in secretory cells.

    Evidence Anti-MADD antibody inhibition in permeabilized parotid acinar cells; GTP-Rab27 pulldown; amylase secretion assay

    PMID:23702376

    Open questions at the time
    • In vitro GEF activity with purified MADD on Rab27a was not demonstrated in this study
    • Whether MADD is the sole GEF for Rab27a across tissues was unknown
    • No structural basis for the MADD–Rab27 interaction was provided
  12. 2014 High

    Selective GAP-mediated inactivation of Rab27a in β-cells showed that nucleotide cycling controls the size of immediately and readily releasable insulin granule pools, placing RAB27A at the rate-limiting priming step of insulin exocytosis.

    Evidence EPI64A GAP overexpression in ashen and WT β-cells; membrane capacitance electrophysiology

    PMID:24909540

    Open questions at the time
    • The endogenous GAP for Rab27a in β-cells was not identified
    • How Rab27a cycling intersects with Rab3a in the same granule pool was unclear
  13. 2014 High

    Demonstration that specific RAB27A mutations (R141, Y159, S163) selectively disrupt Munc13-4 binding while preserving melanophilin binding explained why some patients present with HLH but not albinism, establishing that Rab27a engages its effectors through structurally separable interfaces.

    Evidence Mutagenesis, proximity ligation assay for Rab27a–Munc13-4, confocal imaging of granzyme B polarization, NK cell functional assays

    PMID:25312756 PMID:26880764

    Open questions at the time
    • Full mapping of effector-specific binding surfaces on Rab27a was incomplete
    • Whether additional effectors are affected by these mutations was not tested
  14. 2014 High

    Showing that the GTPase-deficient Q78L mutant fails to reach melanosomes and traps melanophilin in the cytosol resolved a paradox: GTPase activity is required not to trigger transport but to achieve correct organelle targeting of Rab27a itself.

    Evidence Expression of Rab27A(Q78L) with and without melanosome-targeting tag in melanocytes; colocalization and melanosome distribution assays

    PMID:24584932

    Open questions at the time
    • The mechanism by which GTP hydrolysis enables melanosome membrane insertion was not defined
    • The role of GDI recycling in this process was not addressed
  15. 2018 High

    Discovery that Rab27A-GTP recruits Rabphilin3a, which in turn recruits GRAB (a Rab3A GEF) in sperm, established a Rab GEF cascade in which Rab27A activation hierarchically drives Rab3A activation during acrosomal exocytosis.

    Evidence Active Rab27A pulldown from sperm, antibody perturbation in permeabilized sperm, in vitro GEF assay with purified GRAB toward Rab3A, proximity ligation assay

    PMID:30599141

    Open questions at the time
    • Whether this Rab27A→Rab3A cascade operates in other secretory cells was unknown
    • The signal that activates Rab27A upstream in sperm was not identified
  16. 2019 High

    Identification of KIBRA as a stabilizer that protects Rab27a from ubiquitin-proteasomal degradation revealed a post-translational regulatory layer controlling Rab27a protein levels and consequently exosome secretion.

    Evidence Co-IP, ubiquitination assay, proteasome inhibitor rescue, KIBRA KO mouse brain proteomics, siRNA and overexpression with exosome quantification

    PMID:30967557

    Open questions at the time
    • The E3 ubiquitin ligase targeting Rab27a was not identified
    • Whether KIBRA-mediated stabilization is tissue-specific was not tested
  17. 2020 High

    Discovery that Rab27a recruits SPIRE1 actin nucleators to melanosomes, cooperating with formin-1 to build the very actin tracks on which myosin Va transports the organelle, unified the motor-recruitment and track-assembly functions as dual outputs of a single Rab27a platform.

    Evidence Identification of SPIRE1 as Rab27a effector; SPIRE1/formin-1 KO/KD in melanocytes; live imaging of melanosome dynamics

    PMID:32661310

    Open questions at the time
    • Whether SPIRE1 recruitment is coordinated or competitive with melanophilin binding was not resolved
    • Structural basis of Rab27a–SPIRE1 interaction was not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the identity of the E3 ligase targeting Rab27a for ubiquitination, the structural basis for how a single Rab27a surface selectively engages its diverse effectors, the endogenous GAPs in most secretory cell types, and whether the Rab27A→Rab3A GEF cascade is a general secretory principle.
  • E3 ubiquitin ligase for Rab27a unknown
  • No co-crystal structures of Rab27a with Munc13-4, MyRIP, or SPIRE1
  • Endogenous GAPs for Rab27a in most cell types unidentified
  • Generality of Rab27a→Rab3a GEF cascade untested beyond sperm

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0003924 GTPase activity 3
Localization
GO:0031410 cytoplasmic vesicle 5 GO:0043226 organelle 4 GO:0005856 cytoskeleton 3 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 6 R-HSA-168256 Immune System 4 R-HSA-109582 Hemostasis 3 R-HSA-162582 Signal Transduction 2
Partners
MLPHMYO5AMYRIPRPH3ASPIRE1SYTL4UNC13DWWC1
Complex memberships
Rab27a–Munc13-4 complexRab27a–MyRIP–actin complexRab27a–melanophilin–myosin Va tripartite complex

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 RAB27A (Ram/Rab27) is selectively unprenylated in choroideremia lymphoblasts due to preferential dependence on REP-1 over REP-2 for geranylgeranylation; in vitro prenylation assays confirmed REP-1 geranylgeranyl transferase acts on Rab27 more efficiently than REP-2. In vitro geranylgeranylation assay with recombinant Rab geranylgeranyl transferase and REPs; protein purification and identification from choroideremia lymphoblasts The Journal of biological chemistry High 7592656
2001 RAB27A is required for a late step (docking/fusion) of lytic granule exocytosis in cytotoxic T lymphocytes and NK cells; Rab27a colocalizes with granzyme B-positive granules and its loss (ashen mice) abolishes regulated granule secretion while leaving constitutive IFN-γ secretion intact. Loss-of-function in ashen (Rab27a-deficient) mice; cytotoxicity assays, anti-CD3-stimulated granule secretion assay, immunolocalization of Rab27a with granzyme B granules The Journal of cell biology High 11266473
2002 Slac2-a/melanophilin is the 'missing link' bridging GTP-Rab27A on melanosomes to myosin Va, forming a tripartite Rab27A·Slac2-a·myosin Va complex required for melanosome transport; the N-terminal SHD of Slac2-a binds Rab27A/B and the C-terminal half binds the 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 Melanophilin (a Rab27-binding protein) associates simultaneously with GTP-Rab27a and myosin Va via distinct domains, linking activated Rab27a on melanosomes to myosin Va; overexpression of the Rab27-binding domain alone causes perinuclear melanosome clustering, indicating dominant-negative interference with Rab27a function. Yeast two-hybrid screen, GST pulldown, co-immunoprecipitation, overexpression in melanocytes with melanosome distribution readout The Journal of biological chemistry High 11980908
2002 RAB27A is an essential component of the melanosome receptor for myosin Va; myosin Va requires its alternatively spliced exon F (not exon D) to associate with Rab27a on melanosomes, the interaction is GTP-dependent, and an additional bridging protein (later identified as melanophilin) is required since pure Rab27a does not bind myosin Va directly. Pulldown with purified myosin Va isoforms (exon F/D deletions), co-IP from melanocyte lysates with GDP vs. GTPγS, rescue of dilute phenotype in melanocytes Molecular biology of the cell High 12006666
2002 Rab27b is functionally redundant with Rab27a in platelet dense granules and can rescue ashen (Rab27a-null) coat colour when transgenically expressed; Rab27a and Rab27b both localize to the limiting membrane of platelet dense granules. Transgenic rescue of ashen mice with Rab27a or Rab27b; melanosome distribution rescue in ashen melanocytes; subcellular fractionation/immunolocalization in platelets The Journal of clinical investigation High 12122117
2002 Specific Rab27a missense mutations (Trp73Gly, Ala152Pro, Leu130Pro) causing Griscelli syndrome disrupt effector interaction: Trp73Gly retains GTPase characteristics of constitutively active Rab27a but cannot bind melanophilin, abolishing melanosome transport and granule exocytosis. Ala152Pro and Leu130Pro disrupt GTP/GDP binding by affecting protein folding. Site-directed mutagenesis, GTP/GDP-binding assays, co-immunoprecipitation with melanophilin, melanosome distribution assay, cytotoxic granule exocytosis assay Blood High 12446441
2003 Munc13-4 is a GTP-Rab27A/B-binding effector in platelets that regulates dense core granule secretion; recombinant Munc13-4 directly binds GTP-Rab27A in vitro and rescues secretion inhibited by unprenylated Rab27A in permeabilized platelets. Affinity purification from platelets, in vitro binding with recombinant proteins, permeabilized platelet secretion assay with Munc13-4 rescue The Journal of biological chemistry High 14699162
2003 Rab27a and its effector Slac2c/MyRIP regulate the final steps of insulin exocytosis in pancreatic beta-cells; Slac2c/MyRIP interacts with cortical actin (the actin-binding domain of Slac2c is required for this function) and its silencing impairs secretagogue-stimulated, but not basal, insulin release. RNAi knockdown, overexpression of domain mutants abolishing actin binding, insulin secretion assay in beta-cells Molecular biology of the cell High 14517322
2006 Rab7 controls microtubule-mediated transport of early/intermediate melanosomes while Rab27a (in its active GTP-bound state) controls subsequent actin-dependent transport of mature melanosomes via myosin Va; the two GTPases thus regulate sequential and complementary phases of melanosome transport. Colocalization studies, immunostaining of Rab7 and Rab27a on melanosomes at different maturation stages, analysis in melanocytes Pigment cell research Medium 16965270
2006 In platelets, Rab27 is maintained predominantly in the GTP-bound form by constitutive GDP/GTP exchange in resting conditions; upon secretion, GTP hydrolysis by Rab27 is enhanced but is not itself required to trigger secretion (non-hydrolyzable GTP analogue does not block secretion). TLC nucleotide analysis from immunoprecipitated Rab27, pulldown with Slp homology domain of Slac2-b, GppNHp loading in permeabilized platelets with Ca2+-induced secretion assay The Journal of biological chemistry High 16880209
2007 Rab27a controls phagosomal pH and NADPH oxidase (NOX2) recruitment in dendritic cells; Rab27a-deficient dendritic cells show increased phagosome acidification and antigen degradation due to delayed recruitment of NOX2-containing lysosome-related organelles to phagosomes, causing a defect in antigen cross-presentation. Rab27a-deficient ashen mouse-derived DCs; phagosomal pH measurements, NOX2 recruitment assay, cross-presentation assay Nature cell biology High 17351642
2007 Rab27A and Rab3A show distinct dynamics on secretory granules in PC12 cells: Rab3A exchanges rapidly between granules and cytosol while Rab27A remains stably associated with granules; both Rabs associate preferentially with newly synthesized granules after TGN release. FRAP of EGFP-Rab27A and EGFP-Rab3A on secretory granules in PC12 cells; colocalization with secretogranin II Journal of cell science Medium 17311845
2008 The crystal structure of the constitutively active Rab27B·GTP complex with the effector domain of Slac2-a/melanophilin revealed specific intermolecular hydrogen bonds that confer exclusive Rab27 subfamily specificity; transplanting four Rab27-specific residues into Rab3A conferred Slac2-a binding ability. Crystal structure determination; mutagenesis of Rab27A and Rab3A; in vitro binding assays Structure (London, England : 1993) High 18940604
2009 Rab27a and Rab27b control distinct steps of exosome secretion: Rab27a silencing increases MVE size (controlling MVE docking/size at the plasma membrane), while Rab27b silencing redistributes MVEs to a perinuclear region; their effectors Slp4/SYTL4 and Slac2b/EXPH5 phenocopy these effects respectively. RNAi screen in HeLa cells; siRNA silencing of Rab27a, Rab27b, Slp4, Slac2b; exosome secretion quantification; electron microscopy of MVE size and distribution Nature cell biology High 19966785
2009 Rab27a and its effector MyRIP anchor mature Weibel-Palade bodies (WPBs) to peripheral actin in endothelial cells; depletion of either increases basal and stimulated VWF secretion and results in shorter, less multimerized VWF strings, indicating the complex restrains premature WPB release. siRNA depletion in primary endothelial cells; VWF secretion quantification; immunolocalization; VWF string length measurement under flow Blood High 19270261
2009 Rab27a and Rab27b independently regulate azurophilic granule exocytosis and NADPH oxidase activation at the plasma membrane in neutrophils; TIRF microscopy showed both Rab27a- and Rab27b-deficient neutrophils have fewer azurophilic granules near the plasma membrane, with additive defects in double KO cells. Rab27a(ash/ash), Rab27b KO, and Rab27a/b double KO mice; TIRF microscopy; granule exocytosis assays; NADPH oxidase activity assay Traffic (Copenhagen, Denmark) High 20028487
2013 MADD/DENN/Rab3GEP functions as a guanine nucleotide exchange factor (GEF) for Rab27 in rat parotid acinar cells; anti-MADD antibody introduced into permeabilized acinar cells inhibited isoproterenol-induced amylase release and reduced GTP-Rab27 levels. RT-PCR for DENN family expression; antibody inhibition in streptolysin O-permeabilized parotid acinar cells; GTP-Rab27 pulldown assay; amylase secretion assay Archives of biochemistry and biophysics Medium 23702376
2014 Rab27A GTP/GDP nucleotide cycling is essential for generation of the immediately releasable pool (IRP) of insulin secretory granules and regulation of the readily releasable pool (RRP) size in pancreatic beta-cells, as shown by selective inactivation of Rab27A using EPI64A GAP in ashen and wild-type beta-cells. Rab3GAP and EPI64A GAP overexpression in ashen and WT beta-cells; membrane capacitance measurements of exocytosis Traffic (Copenhagen, Denmark) High 24909540
2014 Specific RAB27A mutations (at R141, Y159, or S163) selectively disrupt the Rab27a–Munc13-4 interaction without impairing the Rab27a–melanophilin interaction, causing HLH without albinism; the A87P mutation reduces Munc13-4 binding and delays granzyme B polarization to the immunological synapse. Mutagenesis; proximity ligation assay for Rab27A–Munc13-4 interaction; confocal microscopy of granzyme B polarization; NK cell cytotoxicity and degranulation assays The Journal of allergy and clinical immunology / Journal of immunology (Baltimore, Md. : 1950) High 25312756 26880764
2016 Rab27A regulates cortical granule (CG) exocytosis during mouse oocyte activation at the MII stage; antibody microinjection against Rab27A inhibits CG exocytosis following oocyte activation. Antibody microinjection into mouse MII oocytes; CG exocytosis assay; immunolocalization of Rab27A in oocytes Histochemistry and cell biology Medium 26791531
2018 IRF-1 transcriptionally regulates Rab27a expression by binding to functional motifs in the Rab27a promoter; IFN-γ stimulation or IR induces IRF-1 and consequently Rab27a expression and EV secretion, and IRF-1 silencing decreases Rab27a and EV secretion. ChIP, EMSA, Rab27a promoter luciferase assay; siRNA knockdown in vitro; liver IR model in vivo Hepatology (Baltimore, Md.) High 29059701
2018 Rab27A-GTP interacts with Rabphilin3a in human sperm, which in turn recruits GRAB (a GEF for Rab3A), establishing a RabGEF cascade where Rab27A activation precedes and drives Rab3A activation during acrosomal exocytosis. Active Rab27A pulldown from sperm extracts; antibody sequestration in streptolysin O-permeabilized sperm; in vitro GEF assay with purified GRAB toward Rab3A; proximity ligation assay Biochimica et biophysica acta. Molecular cell research High 30599141
2019 KIBRA stabilizes Rab27a protein by preventing its ubiquitination and proteasomal degradation; KIBRA directly interacts with Rab27a, and KIBRA knockdown/overexpression decreases/increases exosome secretion and alters MVB size, with reduced Rab27a protein in KIBRA-KO mouse brain. Co-IP, ubiquitination assay, proteasome inhibitor rescue, KIBRA KO mouse brain proteomics, siRNA knockdown and overexpression with exosome quantification Nature communications High 30967557
2020 Rab27a recruits SPIRE-type actin nucleators (predominantly SPIRE1) as effectors to melanosomes, cooperating with formin-1 to generate actin tracks required for myosin-Va-dependent long-range melanosome dispersion; Rab27a thus integrates both motor (via melanophilin/myosin-Va) and actin track assembly (via SPIRE1) at the organelle membrane. Identification of SPIRE1 as Rab27a effector; functional co-operation assays in melanocytes; KO/KD experiments for SPIRE1, formin-1, Rab27a; live imaging of melanosome dynamics Nature communications High 32661310
2010 Loss of both Rab27a and Rab27b in the murine lung causes accumulation of mature lamellar bodies in alveolar epithelial type II cells (without immature precursors) and vesicle accumulation in Clara cells, indicating Rab27 GTPases regulate surfactant secretion through the secretory pathway of these lung epithelial cells. Rab27a/b double KO mice; light and electron microscopy of lung ultrastructure; immunohistochemistry American journal of physiology. Cell physiology Medium 21160031
2014 The GTPase-deficient Rab27A(Q78L) mutant fails to localize to mature melanosomes and inhibits melanosome transport by trapping the effector Slac2-a/melanophilin in the cytosol, preventing it from reaching melanosomes; GTPase activity is required for melanosome localization but not for transport per se. Expression of Rab27A(Q78L) with and without MST melanosome-targeting tag in melanocytes; colocalization studies; melanosome distribution assay The Journal of biological chemistry High 24584932

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 2134 19966785
2015 A Rare Allele of GS2 Enhances Grain Size and Grain Yield in Rice. Molecular plant 345 26187814
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 299 11856727
2002 A family of Rab27-binding proteins. Melanophilin links Rab27a and myosin Va function in melanosome transport. The Journal of biological chemistry 268 11980908
2014 Cellular disposal of miR23b by RAB27-dependent exosome release is linked to acquisition of metastatic properties. Cancer research 243 25261234
2001 Defective granule exocytosis in Rab27a-deficient lymphocytes from Ashen mice. The Journal of cell biology 206 11266473
2007 Rab27a regulates phagosomal pH and NADPH oxidase recruitment to dendritic cell phagosomes. Nature cell biology 205 17351642
1995 Deficient geranylgeranylation of Ram/Rab27 in choroideremia. The Journal of biological chemistry 196 7592656
2013 Rab27 effectors, pleiotropic regulators in secretory pathways. Traffic (Copenhagen, Denmark) 193 23678941
2019 KIBRA controls exosome secretion via inhibiting the proteasomal degradation of Rab27a. Nature communications 190 30967557
2005 Versatile role of Rab27 in membrane trafficking: focus on the Rab27 effector families. Journal of biochemistry 189 15713878
2003 Munc13-4 is a GTP-Rab27-binding protein regulating dense core granule secretion in platelets. The Journal of biological chemistry 162 14699162
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 140 12006666
2003 Involvement of the Rab27 binding protein Slac2c/MyRIP in insulin exocytosis. Molecular biology of the cell 135 14517322
2018 Circ-BPTF promotes bladder cancer progression and recurrence through the miR-31-5p/RAB27A axis. Aging 106 30103209
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 90 30556600
2009 Rab27a and Rab27b regulate neutrophil azurophilic granule exocytosis and NADPH oxidase activity by independent mechanisms. Traffic (Copenhagen, Denmark) 88 20028487
2009 Rab27a and MyRIP regulate the amount and multimeric state of VWF released from endothelial cells. Blood 87 19270261
2017 Rab27-Dependent Exosome Production Inhibits Chronic Inflammation and Enables Acute Responses to Inflammatory Stimuli. Journal of immunology (Baltimore, Md. : 1950) 84 28978688
2016 Evidence of melatonin synthesis in the ram reproductive tract. Andrology 75 26742835
2008 RAM-induced allostery facilitates assembly of a notch pathway active transcription complex. The Journal of biological chemistry 75 18381292
2016 A Heterozygous RAB27A Mutation Associated with Delayed Cytolytic Granule Polarization and Hemophagocytic Lymphohistiocytosis. Journal of immunology (Baltimore, Md. : 1950) 74 26880764
2006 Rab7 and Rab27a control two motor protein activities involved in melanosomal transport. Pigment cell research 74 16965270
2012 Differential expression of Rab27A/B correlates with clinical outcome in hepatocellular carcinoma. World journal of gastroenterology 72 22553406
2002 Biochemical and functional characterization of Rab27a mutations occurring in Griscelli syndrome patients. Blood 69 12446441
2018 Functional implications of Rab27 GTPases in Cancer. Cell communication and signaling : CCS 68 30081925
2006 Rab27 and its effectors in secretory granule exocytosis: a novel docking machinery composed of a Rab27.effector complex. Biochemical Society transactions 64 17052176
2022 Phytosulfokine peptide optimizes plant growth and defense via glutamine synthetase GS2 phosphorylation in tomato. The EMBO journal 60 36562188
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
1967 Amino acids in ram testicular fluid and semen and their metabolism by spermatozoa. The Biochemical journal 58 16742531
2008 Structural basis for the exclusive specificity of Slac2-a/melanophilin for the Rab27 GTPases. Structure (London, England : 1993) 57 18940604
2007 Differential dynamics of Rab3A and Rab27A on secretory granules. Journal of cell science 56 17311845
2018 Supplementation of ram semen extender to improve seminal quality and fertility rate. Animal reproduction science 54 29615291
2007 Physiological roles of Rab27 effectors in regulated exocytosis. Endocrine journal 53 17664848
2018 Interferon regulatory factor 1-Rab27a regulated extracellular vesicles promote liver ischemia/reperfusion injury. Hepatology (Baltimore, Md.) 52 29059701
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) 47 18768832
2001 The chloroplastic glutamine synthetase (GS-2) of tobacco is phosphorylated and associated with 14-3-3 proteins inside the chloroplast. Planta 46 11506362
2020 Rab27a co-ordinates actin-dependent transport by controlling organelle-associated motors and track assembly proteins. Nature communications 45 32661310
2017 Melatonin MT₁ and MT₂ Receptors in the Ram Reproductive Tract. International journal of molecular sciences 44 28335493
2018 Effect of Heat Stress on Sperm DNA: Protamine Assessment in Ram Spermatozoa and Testicle. Oxidative medicine and cellular longevity 42 29765499
2014 Patients with Griscelli syndrome and normal pigmentation identify RAB27A mutations that selectively disrupt MUNC13-4 binding. The Journal of allergy and clinical immunology 40 25312756
2010 Tales of RAM and MOR: NDR kinase signaling in fungal morphogenesis. Current opinion in microbiology 39 20869909
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
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 38 34258777
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
2009 Caffeine induces ram sperm hyperactivation independent of cAMP-dependent protein kinase. International journal of andrology 35 19845799
2017 Effects of Rab27A and Rab27B on Invasion, Proliferation, Apoptosis, and Chemoresistance in Human Pancreatic Cancer Cells. Pancreas 34 28902788
2019 Melatonin reduces cAMP-stimulated capacitation of ram spermatozoa. Reproduction, fertility, and development 33 30209004
2014 Distinct actions of Rab3 and Rab27 GTPases on late stages of exocytosis of insulin. Traffic (Copenhagen, Denmark) 32 24909540
2021 In vivo Roles of Rab27 and Its Effectors in Exocytosis. Cell structure and function 31 34483204
2020 Exogenous melatonin advances the ram breeding season and increases testicular function. Scientific reports 31 32546776
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
2020 Optical RAM and integrated optical memories: a survey. Light, science & applications 29 32509298
2011 The glutamine synthetase (GS2) genes in relation to grain protein content of durum wheat. Functional & integrative genomics 29 21755355
1994 Isolation of a new gene GS2 (DXS1283E) from a CpG island between STS and KAL1 on Xp22.3. Genomics 29 7806223
2021 Proteomic fertility markers in ram sperm. Animal reproduction science 28 34823050
2017 Rab27A overexpression promotes bladder cancer proliferation and chemoresistance through regulation of NF-κB signaling. Oncotarget 28 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 28 27076615
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
2002 Single-cell protein production from ram horn hydrolysate by bacteria. Bioresource technology 27 12227535
2005 Rab27a: a new face in beta cell metabolism-secretion coupling. The Journal of clinical investigation 26 15690078
1978 Electrophysiology of the afferent innervation of the penis of the domestic ram. The Journal of physiology 26 722579
2023 RELAY, Ramucirumab Plus Erlotinib (RAM+ERL) in Untreated Metastatic EGFR-Mutant NSCLC (EGFR+ NSCLC): Association Between TP53 Status and Clinical Outcome. Clinical lung cancer 25 37076395
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
2017 ACR11 is an Activator of Plastid-Type Glutamine Synthetase GS2 in Arabidopsis thaliana. Plant & cell physiology 25 28339983
2016 Rab3A, Rab27A, and Rab35 regulate different events during mouse oocyte meiotic maturation and activation. Histochemistry and cell biology 25 26791531
2023 Resveratrol Improves the Frozen-Thawed Ram Sperm Quality. Animals : an open access journal from MDPI 23 38136923
2021 NADPH Oxidase 5 and Melatonin: Involvement in Ram Sperm Capacitation. Frontiers in cell and developmental biology 23 34026754
2021 miR-4454 Promotes Hepatic Carcinoma Progression by Targeting Vps4A and Rab27A. Oxidative medicine and cellular longevity 23 34777698
2020 Griscelli Syndrome Type 2 Sine Albinism: Unraveling Differential RAB27A Effector Engagement. Frontiers in immunology 23 33362801
2018 DNA fragmentation in epididymal freeze-dried ram spermatozoa impairs embryo development. The Journal of reproduction and development 23 29973438
2014 A role for Rab27 in neutrophil chemotaxis and lung recruitment. BMC cell biology 23 25359237
2021 Trehalose modifies the protein profile of ram spermatozoa during cryopreservation. Theriogenology 22 34000687
2022 Necroptosis is associated with Rab27-independent expulsion of extracellular vesicles containing RIPK3 and MLKL. Journal of extracellular vesicles 21 36063142
2021 Platelet-rich plasma promotes MSCs exosomes paracrine to repair acute kidney injury via AKT/Rab27 pathway. American journal of translational research 20 33841669
2018 Rab27a Regulates Human Perivascular Adipose Progenitor Cell Differentiation. Cardiovascular drugs and therapy 20 30105417
2002 Rapid degradation of dominant-negative Rab27 proteins in vivo precludes their use in transgenic mouse models. BMC cell biology 20 12401133
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 19 36303180
2018 Linc-RAM is required for FGF2 function in regulating myogenic cell differentiation. RNA biology 19 29364044
2014 The GTPase-deficient Rab27A(Q78L) mutant inhibits melanosome transport in melanocytes through trapping of Rab27A effector protein Slac2-a/melanophilin in their cytosol: development of a novel melanosome-targetinG tag. The Journal of biological chemistry 19 24584932
2008 The Rab27 effector Rabphilin, unlike Granuphilin and Noc2, rapidly exchanges between secretory granules and cytosol in PC12 cells. Biochemical and biophysical research communications 18 18573236
2018 Grab recruitment by Rab27A-Rabphilin3a triggers Rab3A activation in human sperm exocytosis. Biochimica et biophysica acta. Molecular cell research 17 30599141
2017 Downregulation of Rab27A contributes to metformin-induced suppression of breast cancer stem cells. Oncology letters 17 28928832
2015 Rab27A Is Present in Mouse Pancreatic Acinar Cells and Is Required for Digestive Enzyme Secretion. PloS one 17 25951179
2011 Rab27a in pancreatic beta-cells, a busy protein in membrane trafficking. Progress in biophysics and molecular biology 17 21762718
2010 Rab27a, actin and beta-cell endocytosis. Endocrine journal 17 21187662
2009 GS2 as a retinol transacylase and as a catalytic dyad independent regulator of retinylester accretion. Molecular genetics and metabolism 17 19181555
2018 Siglec expression on the surface of human, bull and ram sperm. Reproduction (Cambridge, England) 16 29581386
2018 Immunization against Kisspeptin-54 perturb hypothalamic-pituitary-testicular signaling pathway in ram lambs. Theriogenology 16 30465983
2016 Rab27a/Slp2-a complex is involved in Schwann cell myelination. Neural regeneration research 16 28123429
2022 The Cryopreserved Sperm Traits of Various Ram Breeds: Towards Biodiversity Conservation. Animals : an open access journal from MDPI 15 35625160
2010 Loss of Rab27 function results in abnormal lung epithelium structure in mice. American journal of physiology. Cell physiology 15 21160031