Affinage

RAB27B

Ras-related protein Rab-27B · UniProt O00194

Length
218 aa
Mass
24.6 kDa
Annotated
2026-06-10
86 papers in source corpus 41 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAB27B is a small Rab GTPase that functions as a GTP-dependent molecular switch controlling the docking, transport, and fusion of secretory granules, secretory lysosomes, multivesicular endosomes, and specialized apical vesicles with the plasma membrane across a broad range of secretory cell types (PMID:19966785, PMID:15039459, PMID:20028487). It associates with diverse organelle membranes—dense-core and dense/alpha granules in pituitary, platelet, and megakaryocyte lineages (PMID:17384153, PMID:11956164, PMID:12907454), zymogen granules in pancreatic acinar cells (PMID:15451418, PMID:26845357), synaptic vesicles in neurons (PMID:20926670), melanosomes (PMID:12060386), and fusiform/discoidal vesicles in urothelium (PMID:14625374, PMID:29167152)—and engages effector proteins to execute distinct steps of regulated exocytosis: Slac2-c/MyRIP and granuphilin on secretory granules (PMID:15039459, PMID:11956164), Slp1 and Slp3 on zymogen and mast-cell granules (PMID:18477466, PMID:27810912), Slac2-b/EXPH5 on multivesicular endosomes and keratinocyte vesicles (PMID:19966785, PMID:23176819), Munc13-4 at the final fusion step in mast cells and osteoblasts (PMID:20939018, PMID:23281710), and melanophilin/MyoVa for actin-based melanosome transport (PMID:15357836). Through sequential motor coupling—kinesin-1 via Slp3 for microtubule-based transport and myosin Va/5C for actin-based delivery—RAB27B governs the handoff of vesicles from microtubule to cortical-actin tracks toward the secretion site (PMID:23281710, PMID:27810912, PMID:22363735). Its activity cycle is set by the GEF MADD/Rab3GEP and the GAP EPI64B/TBC1D10B, with Rab-GDI extracting GDP-bound RAB27B from membranes after exocytosis, and membrane association requires geranylgeranylation (PMID:23671284, PMID:33845096, PMID:19583748, PMID:20484105). Genetic loss of RAB27B causes a bleeding phenotype with impaired platelet dense-granule secretion in mice (PMID:17384153), and mutation of its effector EXPH5 causes inherited skin fragility in humans (PMID:23176819). Beyond secretion, RAB27B promotes lysosomal enzyme maturation and autophagic flux required for α-synuclein clearance in neurons (PMID:32350025, PMID:39965930), drives invasive growth and exosome/extracellular-vesicle cargo secretion (HSP90α, MMP-2 activation) in cancer (PMID:20484105, PMID:23390068, PMID:39723610), and controls NRAS palmitoylation and plasma-membrane trafficking through physical interaction with the palmitoyl acyltransferase ZDHHC9 to sustain RAS/ERK signaling and leukemogenesis (PMID:37317963, PMID:39899936).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2002 High

    Established RAB27B as a regulator of regulated dense-core granule exocytosis, showing it acts on the secretory pathway rather than being a passive granule marker.

    Evidence Co-IP with granuphilin and dominant-negative N133I mutant inhibiting ACTH secretion in AtT20 pituitary cells; dominant-negative effects on melanosome positioning in melanocytes

    PMID:11956164 PMID:12060386

    Open questions at the time
    • Endogenous activity cycle (GEF/GAP) not yet defined
    • Melanocyte role rests on dominant-negative overexpression rather than genetic loss
  2. 2004 High

    Identified the RAB27B–effector module on secretory granules, showing the GTPase requires effector binding to drive exocytosis.

    Evidence Reciprocal Co-IP of Rab27B with Slac2-c/MyRIP and functional disruption of amylase release in parotid acinar cells; constitutive-active/dominant-negative mutants modulating zymogen granule exocytosis in pancreatic acini

    PMID:15039459 PMID:15451418

    Open questions at the time
    • Whether effectors mediate docking versus fusion not resolved
    • Structural basis of effector recognition unknown
  3. 2007 High

    Genetic knockout defined non-redundant physiological roles of RAB27B in secretion and revealed partial overlap with RAB27A.

    Evidence Rab27b KO mice showing hemorrhagic disease and reduced platelet dense-granule number/secretion; mast cell degranulation and anaphylaxis defects; double-KO granule mislocalization in pituitary; crystal structure of Rab27b-GDP

    PMID:17384153 PMID:17582168 PMID:17587407 PMID:17761531

    Open questions at the time
    • Molecular basis of RAB27A vs RAB27B effector specificity unresolved despite structure
    • Granule-number defect mechanism (packaging) not mechanistically dissected
  4. 2009 High

    Placed RAB27B in the exosome/MVE secretion pathway and in granule docking, distinguishing it from RAB27A at the molecular step level.

    Evidence RNAi screen showing RAB27B controls MVE docking with EXPH5/Slac2b phenocopy; TIRF microscopy of azurophilic granule docking in neutrophil KO; temporal GDI-extraction of Rab27B in parotid cells

    PMID:19583748 PMID:19966785 PMID:20028487

    Open questions at the time
    • Mechanism distinguishing RAB27A and RAB27B docking steps not fully defined
    • GDI-extraction shown by Co-IP/localization without direct functional perturbation
  5. 2011 Medium

    Resolved the order of RAB27B action as the final vesicle-fusion step and mapped sequential motor recruitment for vesicle delivery.

    Evidence RNAi of Rab27a/b and Slp4-a/Slp5/Munc13-4 in osteoblastic RANKL release blocking fusion but not docking; KO and gain/loss-of-function in lacrimal acinar cells; live imaging of sequential dynein/Myosin5C recruitment to nascent Rab27b vesicles

    PMID:20939018 PMID:21525430 PMID:22363735

    Open questions at the time
    • Direct demonstration of fusion-machinery engagement (SNAREs) absent
    • Effector knockdowns are single-lab without reciprocal validation
  6. 2013 High

    Defined the RAB27B activity cycle and a genetic epistasis pathway separating RAB27B/Munc13-4 fusion control from RAB27A/Mlph/MyoVa cortical-actin control.

    Evidence EPI64B/TBC1D10B GAP activity assay with active-site mutants and KO-rescue in pancreatic acini; five-KO genetic epistasis in mast cells; human EXPH5 mutation causing skin fragility

    PMID:23176819 PMID:23281710 PMID:23671284

    Open questions at the time
    • Activating GEF still unidentified at this stage
    • How GAP/GEF are spatially targeted to specific organelles unknown
  7. 2016 High

    Connected RAB27B to motor-driven granule transport and to lysosomal/late-endosomal secretory trafficking in distinct cell types.

    Evidence Co-IP of Kif5b/Slp3/Rab27b trimeric complex with PI3K-dependent recruitment and Kif5b KO anaphylaxis defect in mast cells; shRNA showing Rab27b drives PLP lysosomal exocytosis and myelination in oligodendrocytes

    PMID:27325508 PMID:27810912

    Open questions at the time
    • Coupling between kinesin-driven transport and myosin-driven cortical delivery not unified
    • Oligodendrocyte role based on shRNA in a single lab
  8. 2020 High

    Extended RAB27B function from secretion into lysosomal degradative capacity and autophagic flux required for neuronal protein clearance.

    Evidence shRNA and KO/overexpression in neurons measuring αsyn release, solubility, LC3 turnover with chloroquine, lysosomal enzyme maturation, and αsyn fibril seeding; KO electrophysiology defining selective MF-CA3 presynaptic LTP requirement with lentiviral rescue

    PMID:32350025 PMID:32358861 PMID:39965930

    Open questions at the time
    • Effector mediating lysosomal/autophagic role in neurons not identified
    • Direct link between secretory and degradative functions of RAB27B unresolved
  9. 2021 Medium

    Mapped upstream transcriptional and signaling control of RAB27B in cancer secretion and in epithelial defense and disease contexts.

    Evidence CaSR→PI3K/PKA/mTOR→MADD GEF activation driving Rab27B-dependent cytokine secretion; NRF2 and FOXO1 transcriptional regulation of RAB27B in UPEC expulsion and diabetic-kidney exosome secretion

    PMID:33597203 PMID:33845096 PMID:34686330

    Open questions at the time
    • MADD GEF activity on RAB27B inferred from pathway inhibition rather than direct nucleotide-exchange assay
    • Transcriptional axes are single-lab and context-specific
  10. 2023 High

    Revealed a non-canonical RAB27B function regulating RAS posttranslational modification through ZDHHC9, expanding its role beyond vesicle trafficking into oncogenic signaling.

    Evidence Proteomics, Co-IP with ZDHHC9, palmitoylation assays, KO mice and primary human AML depletion showing RAB27B controls NRAS palmitoylation, membrane localization, ERK signaling, and leukemogenesis; MADD/Rab11A endosomal-secretory axis defined; m6A/YTHDF1 mRNA stabilization in CML

    PMID:37317963 PMID:37604243 PMID:37692484

    Open questions at the time
    • Whether ZDHHC9 regulation requires RAB27B GTPase activity not fully defined
    • Mechanism by which RAB27B promotes palmitoyl-transfer (scaffolding vs trafficking) unresolved
  11. 2024 High

    Established RAB27B as a node controlling extracellular-vesicle cargo composition and tumor immune evasion under TGF-β control, and as a self-reinforcing component of NRAS/ERK signaling.

    Evidence TGF-β→SMAD3 ChIP repression of RAB27B with click-chemistry EV proteomics and CD8+ T cell killing assay; NRASQ61R→ERK/C/EBPβ feedback upregulating RAB27B in endothelial cells with MEK inhibition reducing RAB27B

    PMID:39723610 PMID:39899936

    Open questions at the time
    • How RAB27B selectively determines EV cargo identity unknown
    • Generality of the ERK–RAB27B feedback loop across cell types untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single GTPase coordinates its canonical vesicle-fusion machinery with its degradative (lysosomal/autophagic) and non-vesicular (ZDHHC9/NRAS palmitoylation) functions, and what determines effector and organelle selectivity in each context, remains unresolved.
  • No unified structural/biochemical model linking GTP-state to the divergent effector repertoire
  • Determinants of organelle-specific targeting in different cell types undefined
  • Mechanistic coupling between secretory and degradative roles unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0003924 GTPase activity 3
Localization
GO:0031410 cytoplasmic vesicle 6 GO:0005886 plasma membrane 4 GO:0005764 lysosome 3 GO:0005768 endosome 3 GO:0005829 cytosol 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-9609507 Protein localization 4 R-HSA-168256 Immune System 3 R-HSA-109582 Hemostasis 2 R-HSA-162582 Signal Transduction 2 R-HSA-9612973 Autophagy 2
Partners
EXPH5MADDMLPHMYRIPSYTL3TBC1D10BUNC13DZDHHC9
Complex memberships
Kif5b–Slp3–Rab27B complexRab27B–Slac2-c/MyRIP complexRab27B–melanophilin–Myosin Va complex

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 RNAi screen identified RAB27B as a regulator of MVE docking at the plasma membrane for exosome secretion; RAB27B silencing redistributed MVEs toward the perinuclear region, and silencing its effector Slac2b (EXPH5) phenocopied RAB27B knockdown. Thus RAB27B controls a distinct step in the exosomal pathway compared to RAB27A. RNAi screen, siRNA knockdown, fluorescence microscopy, exosome secretion assay Nature cell biology High 19966785
2007 Rab27b knockout mice exhibit hemorrhagic disease, impaired platelet aggregation, and reduced dense granule secretion. A 50% reduction in dense granule number per platelet was observed, suggesting a role in dense granule packaging during megakaryocyte maturation. Rab27a partially compensated for the secretory defect but not the reduced granule number. Knockout mouse generation, in vitro platelet aggregation assay, dense granule secretion assay, electron microscopy Proceedings of the National Academy of Sciences of the United States of America High 17384153
2004 Rab27B localizes to amylase-containing secretory granules in rat parotid acinar cells and forms a complex with the effector Slac2-c/MyRIP on granules. Disruption of the Rab27B–Slac2-c complex (via recombinant Slp homology domain or blocking antibodies) inhibited isoproterenol-stimulated amylase release, establishing this complex as required for secretory granule exocytosis. Subcellular fractionation, immunoprecipitation, immunohistochemistry, introduction of dominant-negative recombinant protein/antibodies in permeabilized cells, amylase release assay Journal of cell science High 15039459
2007 Rab27b and Rab27a are both expressed on mast cell secretory granules. Rab27b KO (but not Rab27a KO) impairs mast cell degranulation as measured by beta-hexosaminidase release in vitro and passive cutaneous anaphylaxis in vivo. Live-cell imaging showed ~10-fold increase in fast granule movement (>1.5 μm/s, nocodazole-sensitive) in double KO cells, suggesting Rab27 regulates the transition from microtubule to actin-based motility. Knockout mice, beta-hexosaminidase release assay, passive cutaneous anaphylaxis, live-cell time-lapse imaging, nocodazole treatment Traffic (Copenhagen, Denmark) High 17587407
2007 Rab27b is widely expressed in secretory cells and neurons. In pituitary cells co-expressing Rab27a, Rab27a/b double KO markedly impairs polarized distribution of secretory granules near the plasma membrane, indicating the Rab27 subfamily delivers granules to the exocytic site. Rab27b KO mouse with LacZ reporter, double KO mouse (crossed with ashen), histology, immunofluorescence of secretory granule distribution Molecular biology of the cell High 17761531
2002 Rab27b associates with secretory granules and interacts with the effector granuphilin in pituitary AtT20 cells. Overexpression of the inactive mutant Rab27b N133I significantly inhibits basal and forskolin-induced ACTH secretion, establishing Rab27b as a regulator of pituitary dense core granule exocytosis. Subcellular fractionation, co-immunoprecipitation, dominant-negative mutant overexpression, ACTH secretion assay Endocrinology High 11956164
2003 Rab27b associates with alpha- and dense granules in megakaryocytes. Rab27b expression is induced during terminal megakaryocyte differentiation in an NF-E2-dependent manner; chromatin immunoprecipitation demonstrated NF-E2 recruitment to the Rab27B promoter. Inhibition of endogenous Rab27 function caused quantitative and qualitative defects in proplatelet formation. Chromatin immunoprecipitation, dominant-negative Rab27 inhibition, immunofluorescence localization, proplatelet formation assay Blood High 12907454
2003 Rab27b associates with fusiform vesicles (but not the apical plasma membrane) in differentiated urothelial umbrella cells at extraordinarily high levels (0.1% of total protein); its expression is greatly reduced in cultured urothelial cells that fail to form fusiform vesicles and produce little uroplakin. This positions Rab27b as a regulator of fusiform vesicle delivery to the apical membrane for uroplakin targeting. Immuno-electron microscopy, Western blot, subcellular fractionation, comparison of differentiated vs cultured urothelial cells Proceedings of the National Academy of Sciences of the United States of America Medium 14625374
2004 Rab27b localizes to zymogen granule (ZG) membranes in pancreatic acinar cells. Constitutively active Rab27b Q78L enhanced CCK-induced amylase release by ~92%, while dominant-negative Rab27b N133I inhibited it by ~53% across all CCK doses, establishing Rab27b as a positive regulator of ZG exocytosis. Proteomics/MALDI-MS identification, Western blot, immunocytochemistry, adenovirus-mediated overexpression of wild-type and mutant Rab27b, amylase release assay Biochemical and biophysical research communications High 15451418
2009 Both Rab27a and Rab27b deficiencies impair azurophilic granule exocytosis in neutrophils by independent mechanisms. TIRF microscopy showed decreased numbers of azurophilic granules near the plasma membrane in single and double KO neutrophils. Rab27b KO also impaired NADPH oxidase activation at the plasma membrane; secretory vesicle exocytosis was unaffected, indicating Rab27 selectively controls granule exocytosis. Knockout mice, azurophilic granule exocytosis assay, TIRF microscopy, NADPH oxidase activity measurement Traffic (Copenhagen, Denmark) High 20028487
2010 Rab27b localizes to synaptic vesicle (SV) membranes in neurons, colocalizing with Rab3a and synaptotagmin at presynaptic terminals. Unlike Rab3a, Rab27b persists on SV membranes after Ca2+-triggered exocytosis and is resistant to GDI-mediated retrieval. Modulation of the Rab27b GTP/GDP switch impairs SV recycling. Quantitative mass spectrometry (iTRAQ), immunoblotting, fluorescence microscopy, GDI extraction assay, GTP/GDP switch manipulation with functional SV recycling assay The Journal of neuroscience : the official journal of the Society for Neuroscience High 20926670
2011 Rab27a and Rab27b are both involved in stimulation-dependent RANKL release from secretory lysosomes in osteoblastic cells. Their effectors Slp4-a, Slp5, and Munc13-4 coordinate this activity. Suppression of Rab27a/b or these effectors blocked vesicle fusion to the plasma membrane but did not prevent RANKL accumulation in lysosomal vesicles near stimulated sites, indicating Rab27b acts at the final fusion step. RNAi knockdown, immunofluorescence, RANKL release assay, in vivo jinx (Munc13-4 KO) mouse bone phenotype Journal of bone and mineral research Medium 20939018
2007 Crystal structure of mouse Rab27b-GDP determined in three lattice forms revealed an unexpected domain-swapped dimer with open switch and interswitch regions. Small-angle X-ray scattering showed an extended monomer in solution, suggesting the flexible switch regions may influence effector binding specificity. X-ray crystallography, small-angle X-ray scattering (SAXS) Acta crystallographica. Section D, Biological crystallography High 17582168
2002 Rab27b colocalizes with the melanosome marker TRP-1 and myosin Va at the cell periphery in melan-a melanocytes. Dominant-negative Rab27b mutants caused redistribution of melanosomes from the cell periphery to the perinuclear region and diminished dendrite number and length, suggesting Rab27b regulates outward melanosome movement and dendritic extension. GFP-tagged wild-type and dominant-negative mutant overexpression, co-localization with TRP-1 and myosin Va by fluorescence microscopy, GTPase activity assay The Journal of investigative dermatology Medium 12060386
2004 In Griscelli syndrome type II melanocytes lacking Rab27a, Rab27b is up-regulated and forms a tripartite complex with melanophilin and exon F–containing Myosin Va isoforms on the melanosome membrane, partially compensating for Rab27a loss. This complex links Rab27b to actin-based melanosome transport. Quantitative RT-PCR, Western blot, immunofluorescence, yeast two-hybrid screening Pigment cell research Medium 15357836
2010 Rab27B promotes invasive growth and metastasis in ER-positive breast cancer cells. Mass spectrometry identified HSP90α in Rab27B-secretory vesicles; HSP90α secretion was Rab27B-dependent and required for MMP-2 activation. All functional responses required GTP-binding and geranylgeranylation of Rab27B. GFP-Rab27B overexpression, point mutants (GTP/GDP and geranylgeranylation defective), siRNA knockdown, mass spectrometry of purified vesicles, MMP-2 activation assay, xenograft mouse model, Matrigel invasion assay Journal of the National Cancer Institute High 20484105
2013 V-ATPase subunits (including V0a1 and V0d1) are identified by mass spectrometry in GFP-Rab27B secretory vesicles from MCF-7 cells. V-ATPase activity controls peripheral localization and size of Rab27B vesicles, and V-ATPase inhibition or subunit knockdown reduces Rab27B-dependent HSP90α secretion, MMP-2 activation, and cell invasion. Mass spectrometry on purified GFP-Rab27B vesicles, Western blot, pharmacological inhibition (bafilomycin A1), siRNA knockdown of V0a1/V0d1, invasion assay, CAM assay International journal of cancer High 23390068
2012 Mutation of the Rab27B effector Slac2-b (EXPH5) in humans causes inherited skin fragility with increased perinuclear vesicles in keratinocytes. Slac2-b co-localizes with Rab27B and β4 integrin at early adhesion initiation sites in spreading keratinocytes, and its loss disrupts keratin cytoskeleton and cell adhesion, placing the Rab27B–Slac2-b complex in keratinocyte vesicle trafficking and adhesion. Whole-exome sequencing, immunostaining of patient skin, shRNA knockdown, co-localization by immunofluorescence, adhesion assay American journal of human genetics High 23176819
2013 In mast cells, Rab27b KO impairs degranulation, while Rab27a KO causes hyper-secretion associated with abnormal cortical F-actin. Munc13-4-deficient (jinx) BMMCs phenocopy the Rab27b KO secretory impairment, while Mlph and MyoVa deficiency phenocopies Rab27a KO. This establishes a pathway: Rab27a/Mlph/MyoVa regulates cortical actin upstream, while Rab27b/Munc13-4 mediates the final exocytosis step. Knockout mice for Rab27a, Rab27b, Mlph, MyoVa, Munc13-4; beta-hexosaminidase release assay; immunofluorescence for F-actin; actin disassembly rescue experiments The FEBS journal High 23281710
2008 Slp1, a putative Rab27 effector, is co-expressed with Rab27b in pancreatic acinar cells, co-localizes on zymogen granules, and co-immunoprecipitates with Rab27b in vivo. Slp1 KO mice show increased zymogen granule accumulation, confirming Slp1 participates with Rab27b in amylase secretion machinery. Co-immunoprecipitation, co-localization by immunofluorescence, Slp1 KO mouse morphological analysis Archives of biochemistry and biophysics Medium 18477466
2013 EPI64B (TBC1D10B) functions as a GTPase-activating protein (GAP) for Rab27B in pancreatic acinar cells. EPI64B overexpression abolished the GTP-bound form of Rab27B without affecting Rab3D, enhanced amylase release in a Rab27B-dependent manner, and GAP-activity mutations abolished this effect. Co-overexpression of EPI64B with Rab27B reversed the inhibitory effect of Rab27B on amylase release. Adenoviral overexpression of EPI64B and mutants, GTP-Rab27B pull-down assay, amylase release assay in KO mouse acini The Journal of biological chemistry High 23671284
2011 Rab27b is enriched on large subapical secretory vesicles in lacrimal gland acinar cells, co-localizing with Rab3D and Myosin 5C. Rab27b KO (but not Rab27a KO) alters vesicle abundance and organization. Constitutively active Rab27b enhances and dominant-negative Rab27b suppresses stimulated secretory protein release. Actin disruption blocked vesicle-plasma membrane fusion but not homotypic fusion. Confocal fluorescence microscopy, transmission electron microscopy of KO mice, adenoviral expression of constitutively active/dominant-negative Rab27b, syncollin-GFP release assay, actin disruption experiments American journal of physiology. Cell physiology High 21525430
2010 Rab27b localizes to tubulovesicle membranes in gastric parietal cells. After stimulation, wild-type and constitutively active Rab27b (Q78L) translocate to the apical membrane, while dominant-negative Rab27b (N133I) does not and almost completely inhibits acid secretion. Mass spectrometry identification in tubulovesicle fractions, adenoviral expression of YFP-tagged WT and mutant Rab27b, fluorescence microscopy of localization, aminopyrine accumulation acid secretion assay Gastroenterology Medium 20888820
2016 Kinesin-1 (Kif5b) is recruited to Rab27b-positive secretory granules via the effector Slp3 in a PI3K-dependent manner upon FcεRI stimulation in mast cells, forming a Kif5b/Slp3/Rab27b complex that drives microtubule-dependent granule translocation to the secretion site. Kif5b KO reduces systemic anaphylaxis and secretory granule translocation without affecting cytokine secretion or microtubule reorganization. Kif5b conditional KO mice, passive systemic anaphylaxis assay, granule translocation imaging, co-immunoprecipitation (Slp3/Kinesin-1/Rab27b), PI3K inhibitor studies The Journal of cell biology High 27810912
2016 Rab27b is involved in PLP trafficking from late endosomes/lysosomes to the cell membrane in oligodendrocytes. Rab27b co-localizes with PLP in late endosomes/lysosomes; shRNA knockdown of Rab27b reduces lysosomal exocytosis, decreases PLP surface expression, and reduces myelin-like membrane formation in neuron co-culture. Co-localization by immunofluorescence, shRNA knockdown, surface PLP quantification, lysosomal exocytosis assay, neuron-oligodendrocyte co-culture myelination assay Neuroscience bulletin Medium 27325508
2017 RAB27B regulates stretch-induced exocytosis of discoidal/fusiform vesicles (DFVs) in bladder umbrella cells. RAB27B-specific shRNA significantly inhibited filling-induced exocytosis of hGH-loaded DFVs. RAB27A shRNA had no effect; RAB27B operates in a pathway parallel to (not dependent on) the RAB11A-RAB8A-MYO5B pathway. shRNA knockdown, whole-bladder exocytosis assay with hGH reporter, dominant-active/dominant-negative RAB11A and RAB8A expression, Squassh image quantification American journal of physiology. Cell physiology High 29167152
2020 Rab27b KD in neurons increases αsyn-mediated paracrine toxicity, reduces αsyn release primarily through nonexosomal pathways, leads to accumulation of insoluble αsyn, increases LC3-positive puncta, and decreases LC3 turnover after chloroquine treatment, indicating that Rab27b is required for autophagic flux and αsyn clearance. shRNA knockdown in paracrine neuronal αsyn model, size-exclusion chromatography, LC3 flux assay with chloroquine, toxicity assay The Journal of biological chemistry Medium 32350025
2023 RAB27B controls NRAS palmitoylation and trafficking to the plasma membrane. RAB27B interacts with the palmitoyl acyltransferase ZDHHC9. RAB27B depletion abrogates mutant NRAS palmitoylation, plasma membrane localization, ERK signaling, and myelomonocytic leukemia development in vivo in mice, establishing RAB27B as a regulator of RAS posttranslational modification upstream of RAF/MEK/ERK. Proteomic studies, RAB27B depletion (shRNA/KO) in cell lines and mice, palmitoylation assay, co-immunoprecipitation with ZDHHC9, ERK signaling assays, in vivo leukemia model, primary human AML depletion The Journal of clinical investigation High 37317963
2021 NRF2 promotes UPEC expulsion from urothelial cells by regulating RAB27B transcription. NRF2 activation reduces intracellular ROS and increases RAB27B expression; loss of NRF2 decreases RAB27B and impairs bacterial expulsion both in vitro and in a mouse UTI model. NRF2 KO cells/mice, RAB27B expression analysis, bacterial burden measurement, NRF2 inducer (dimethyl fumarate) treatment, in vitro and in vivo UTI model Cell reports Medium 34686330
2021 In diabetic kidneys, FOXO1 phosphorylation (inactivation) caused by high glucose leads to downregulation of RAB27B and decreased exosome secretion. Constitutively active non-phosphorylatable FOXO1 restored RAB27B expression and exosome secretion in high-glucose-treated cells, establishing a FOXO1–RAB27B transcriptional axis. High-glucose treatment, FOXO1 constitutively active overexpression, RAB27B overexpression rescue, bioinformatics identification of FOXO1 binding sites, in vivo diabetic mouse model Diabetes Medium 33597203
2021 CaSR activates Rab27B expression and activity via PI3K, PKA, mTOR, and the GEF MADD/Rab3GEP in breast cancer cells, leading to Rab27B-dependent secretion of cytokines including IL-6, IL-1β, IL-8, IP-10, and RANTES. This regulation occurs in cancer cells but not in non-cancerous MCF-10A cells. Pharmacological inhibition of PI3K/PKA/mTOR pathways, MADD identification as GEF, cytokine secretion measurements, Rab27B overexpression/knockdown Biochimica et biophysica acta. Molecular cell research Medium 33845096
2023 Rab11A promotes Rab27B-dependent secretion of chemotactic factors downstream of CaSR. MADD (a GEF for Rab3 and Rab27a/b) is activated by Rab11A and mediates Rab27B activation. Endosomal PI3-kinases (Vps34, PI3KC2α) link Rab11A to Rab27B activation. This establishes an endosomal–secretory axis: CaSR → Rab11A → PI3K → MADD → Rab27B → cytokine secretion. Rab11A/MADD co-immunoprecipitation, PI3K inhibitors, Rab11A/Rab27B dominant-negative/constitutively active mutants, cytokine secretion assays Cellular signalling Medium 37604243
2025 Rab27b KO in neurons results in lysosomal proteolytic defects, reduced lysosomal enzyme maturation and localization, and defects in acidic vesicle trafficking without changes in lysosomal count or pH. KO exacerbates αsyn aggregation upon preformed fibril treatment. Rab27b overexpression enhances lysosomal activity and reduces insoluble αsyn. Rab27b KO mouse, shRNA knockdown, lysosomal activity assays, enzyme maturation/localization by immunofluorescence, αsyn fibril seeding assay, αsyn overexpression in KO mice (AAV model) The Journal of neuroscience : the official journal of the Society for Neuroscience High 39965930
2009 After beta-adrenergic stimulation of parotid acinar cells, Rab27B translocates from secretory granules to the subapical region within 5 min and then dissociates into the cytosol by 30 min. Dissociation is mediated by Rab-GDI, which extracts GDP-bound Rab27B from membranes, as a dramatic increase in the Rab27B-GDI complex in the cytosol was detected at 30 min post-stimulation. Immunofluorescence microscopy (temporal localization), co-immunoprecipitation of Rab27B–GDI complex, subcellular fractionation European journal of oral sciences Medium 19583748
2012 In lacrimal gland acinar cells, Rab27b enrichment occurs early during secretory vesicle formation at a basally-localized 'nascent vesicle site' adjacent to the trans-Golgi network. Microtubule disruption with nocodazole traps nascent Rab27b-enriched vesicles at this site. Upon reaching the subapical region, Rab27b-enriched vesicles acquire Myosin 5C, indicating sequential motor recruitment. YFP-Rab27b live-cell imaging, nocodazole treatment, p150-Glued and Myosin 5C co-localization by confocal microscopy PloS one Medium 22363735
2016 Genetic deletion of Rab27B in pancreatic acinar cells decreases zymogen granule size and moderately reduces digestive enzyme secretion. Expression of Rab3D, Rab27A, and downstream effectors was unaffected, indicating Rab27B is involved in zymogen granule maturation and secretion through a distinct mechanism from Rab3D. Rab27B KO mouse, electron microscopy (granule size), digestive enzyme secretion assay, Western blot Biochemical and biophysical research communications Medium 26845357
2020 RAB27b KO in Rab27b KO mice reduces synaptic frequency facilitation at DG/MF-CA3 synapses and completely eliminates LTP at MF-CA3, without affecting SC-CA1 LTP. LTP was rescued by lentiviral re-expression of human Rab27b in the dentate gyrus, establishing Rab27b as selectively required for presynaptic LTP at MF-CA3 synapses. Rab27b KO mice, electrophysiology at SC-CA1 and DG/MF-CA3 synapses, lentiviral rescue of Rab27b in KO mice Physiological reports Medium 32358861
2024 TGF-β suppresses RAB27B transcription via SMAD3, reducing EV release from breast cancer cells. RAB27B depletion or TGF-β treatment recomposed EV protein cargo; these recomposed EVs inhibited CD8+ T cell-mediated cancer cell killing, establishing a TGF-β→SMAD3→RAB27B axis that controls EV composition and cancer immune evasion. TGF-β treatment, SMAD3 ChIP/transcription reporter, RAB27B siRNA, quantitative click-chemistry proteomics, CD8+ T cell killing assay Journal of extracellular vesicles High 39723610
2023 The m6A writer KIAA1429 stabilizes RAB27B mRNA through the m6A/YTHDF1 axis in CML cells. KIAA1429 knockdown reduces RAB27B mRNA stability and decreases RAB27B protein, thereby reducing drug efflux and proliferation; RAB27B knockdown mimics these effects and promotes apoptosis. KIAA1429 knockdown, RAB27B mRNA stability assay, YTHDF1 interaction, RAB27B siRNA knockdown, proliferation/apoptosis assays Genes & diseases Medium 37692484
2020 In bladder cancer, Rab27b mediates exocytosis of BCG bacteria from urothelial cells via its effector SYTL3. Rab27b knockdown or overexpression inversely modulated intracellular BCG quantity and cytotoxicity; androgen receptor (AR) signaling increases Rab27b expression, which drives BCG exocytosis and resistance to BCG therapy. AR and Rab27b knockdown/overexpression, intracellular BCG quantification, cytotoxicity assay, orthotopic xenograft model, microarray identification of Rab27b as AR target Molecular cancer therapeutics Medium 32737155
2025 RAB27B physically interacts with ZDHHC9 to regulate NRAS palmitoylation and ERK activation in NRAS-mutant endothelial cells. NRASQ61R mutation upregulates RAB27B via the ERK/C/EBPβ transcriptional axis, creating a positive feedback loop that drives enhanced proliferation and migration. MEK1/2 inhibition reduces RAB27B gene expression, while RAB27B knockdown suppresses ERK activation. RAB27B knockdown (siRNA), MEK inhibitor treatment, Western blot for ERK/palmitoylation, C/EBPβ identification as transcription factor downstream of ERK Biochemical and biophysical research communications Medium 39899936

Source papers

Stage 0 corpus · 86 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
2010 Effect of the secretory small GTPase Rab27B on breast cancer growth, invasion, and metastasis. Journal of the National Cancer Institute 198 20484105
2007 Rab27b regulates number and secretion of platelet dense granules. Proceedings of the National Academy of Sciences of the United States of America 151 17384153
2018 ZIP4 Promotes Muscle Wasting and Cachexia in Mice With Orthotopic Pancreatic Tumors by Stimulating RAB27B-Regulated Release of Extracellular Vesicles From Cancer Cells. Gastroenterology 122 30342032
2019 RAB27B-activated secretion of stem-like tumor exosomes delivers the biomarker microRNA-146a-5p, which promotes tumorigenesis and associates with an immunosuppressive tumor microenvironment in colorectal cancer. International journal of cancer 109 30980673
1997 Molecular cloning and characterization of rab27a and rab27b, novel human rab proteins shared by melanocytes and platelets. Biochemical and molecular medicine 105 9066979
2018 miR-34c-5p promotes eradication of acute myeloid leukemia stem cells by inducing senescence through selective RAB27B targeting to inhibit exosome shedding. Leukemia 98 29479064
2004 The small GTPase Rab27B regulates amylase release from rat parotid acinar cells. Journal of cell science 94 15039459
2007 Rab27b regulates mast cell granule dynamics and secretion. Traffic (Copenhagen, Denmark) 92 17587407
2007 Rab27b is expressed in a wide range of exocytic cells and involved in the delivery of secretory granules near the plasma membrane. Molecular biology of the cell 92 17761531
2009 Rab27a and Rab27b regulate neutrophil azurophilic granule exocytosis and NADPH oxidase activity by independent mechanisms. Traffic (Copenhagen, Denmark) 88 20028487
2016 MiR-193a-3p and miR-193a-5p suppress the metastasis of human osteosarcoma cells by down-regulating Rab27B and SRR, respectively. Clinical & experimental metastasis 87 26913720
2010 Quantitative analysis of synaptic vesicle Rabs uncovers distinct yet overlapping roles for Rab3a and Rab27b in Ca2+-triggered exocytosis. The Journal of neuroscience : the official journal of the Society for Neuroscience 86 20926670
2002 Involvement of Rab27b in the regulated secretion of pituitary hormones. Endocrinology 82 11956164
2003 A role for Rab27b in NF-E2-dependent pathways of platelet formation. Blood 78 12907454
2003 Rab27b is associated with fusiform vesicles and may be involved in targeting uroplakins to urothelial apical membranes. Proceedings of the National Academy of Sciences of the United States of America 70 14625374
2015 Rab7a and Rab27b control secretion of endothelial microRNA through extracellular vesicles. FEBS letters 69 26348397
2020 Human multipotent mesenchymal stromal cells cytokine priming promotes RAB27B-regulated secretion of small extracellular vesicles with immunomodulatory cargo. Stem cell research & therapy 65 33317598
2013 Distinct and opposing roles for Rab27a/Mlph/MyoVa and Rab27b/Munc13-4 in mast cell secretion. The FEBS journal 62 23281710
2004 Rab27b localizes to zymogen granules and regulates pancreatic acinar exocytosis. Biochemical and biophysical research communications 59 15451418
2012 Germline Mutation in EXPH5 Implicates the Rab27B Effector Protein Slac2-b in Inherited Skin Fragility. American journal of human genetics 58 23176819
2001 Chromosomal mapping, gene structure and characterization of the human and murine RAB27B gene. BMC genetics 51 11178108
2013 Vacuolar H+ ATPase expression and activity is required for Rab27B-dependent invasive growth and metastasis of breast cancer. International journal of cancer 48 23390068
2008 Intramanchette transport during primate spermiogenesis: expression of dynein, myosin Va, motor recruiter myosin Va, VIIa-Rab27a/b interacting protein, and Rab27b in the manchette during human and monkey spermiogenesis. Asian journal of andrology 47 18478159
2023 RAB27B controls palmitoylation-dependent NRAS trafficking and signaling in myeloid leukemia. The Journal of clinical investigation 45 37317963
2021 NRF2 promotes urothelial cell response to bacterial infection by regulating reactive oxygen species and RAB27B expression. Cell reports 40 34686330
2010 The secretory small GTPase Rab27B as a marker for breast cancer progression. Oncotarget 39 21304180
2004 Rab27b is up-regulated in human Griscelli syndrome type II melanocytes and linked to the actin cytoskeleton via exon F-Myosin Va transcripts. Pigment cell research 39 15357836
2017 MiR-20a-5p promotes radio-resistance by targeting Rab27B in nasopharyngeal cancer cells. Cancer cell international 37 28265202
2016 Kinesin-1 controls mast cell degranulation and anaphylaxis through PI3K-dependent recruitment to the granular Slp3/Rab27b complex. The Journal of cell biology 37 27810912
2020 The GTPase Rab27b regulates the release, autophagic clearance, and toxicity of α-synuclein. The Journal of biological chemistry 34 32350025
2017 Effects of Rab27A and Rab27B on Invasion, Proliferation, Apoptosis, and Chemoresistance in Human Pancreatic Cancer Cells. Pancreas 34 28902788
2020 Oncogenic effects of RAB27B through exosome independent function in renal cell carcinoma including sunitinib-resistant. PloS one 32 32379831
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
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
2002 Rab27b association with melanosomes: dominant negative mutants disrupt melanosomal movement. The Journal of investigative dermatology 30 12060386
2020 Androgen Receptor Signaling Reduces the Efficacy of Bacillus Calmette-Guérin Therapy for Bladder Cancer via Modulating Rab27b-Induced Exocytosis. Molecular cancer therapeutics 28 32737155
2020 Rab27B enhances drug resistance in hepatocellular carcinoma by promoting exosome-mediated drug efflux. Carcinogenesis 27 32390047
2011 Rab27b regulates exocytosis of secretory vesicles in acinar epithelial cells from the lacrimal gland. American journal of physiology. Cell physiology 27 21525430
2016 Rab27b is Involved in Lysosomal Exocytosis and Proteolipid Protein Trafficking in Oligodendrocytes. Neuroscience bulletin 26 27325508
2019 Inactivation of Rab27B-dependent signaling pathway by calycosin inhibits migration and invasion of ER-negative breast cancer cells. Gene 23 31002890
2007 Structure of the small GTPase Rab27b shows an unexpected swapped dimer. Acta crystallographica. Section D, Biological crystallography 23 17582168
2021 FOXO1-Mediated Downregulation of RAB27B Leads to Decreased Exosome Secretion in Diabetic Kidneys. Diabetes 22 33597203
2018 MicroRNA-599 suppresses glioma progression by targeting RAB27B. Oncology letters 22 29963197
2023 Rab27b, a Regulator of Exosome Secretion, Is Associated With Peritoneal Metastases in Gastric Cancer. Cancer genomics & proteomics 20 36581340
2023 RAB27B-regulated exosomes mediate LSC maintenance via resistance to senescence and crosstalk with the microenvironment. Leukemia 20 38036630
2006 Expression of RAB27B is up-regulated in senescent human cells. Mechanisms of ageing and development 20 16620919
2009 Redistribution of small GTP-binding protein, Rab27B, in rat parotid acinar cells after stimulation with isoproterenol. European journal of oral sciences 19 19583748
2008 Expression of Rab27B-binding protein Slp1 in pancreatic acinar cells and its involvement in amylase secretion. Archives of biochemistry and biophysics 18 18477466
2017 RAB27B requirement for stretch-induced exocytosis in bladder umbrella cells. American journal of physiology. Cell physiology 17 29167152
2022 RAB27A and RAB27B Expression May Predict Lymph Node Metastasis and Survival in Patients With Gastric Cancer. Cancer genomics & proteomics 15 35985682
2020 The Small GTPases Rab27b Regulates Mitochondrial Fatty Acid Oxidative Metabolism of Cardiac Mesenchymal Stem Cells. Frontiers in cell and developmental biology 15 32351955
2013 EPI64B acts as a GTPase-activating protein for Rab27B in pancreatic acinar cells. The Journal of biological chemistry 15 23671284
2021 The calcium sensing receptor (CaSR) promotes Rab27B expression and activity to control secretion in breast cancer cells. Biochimica et biophysica acta. Molecular cell research 14 33845096
2017 Overexpression of microRNA-133b reduces myocardial injuries in children with viral myocarditis by targeting Rab27B gene. Cellular and molecular biology (Noisy-le-Grand, France) 14 29096746
2010 Rab27b localizes to the tubulovesicle membranes of gastric parietal cells and regulates acid secretion. Gastroenterology 13 20888820
2023 The m6A regulator KIAA1429 stabilizes RAB27B mRNA and promotes the progression of chronic myeloid leukemia and resistance to targeted therapy. Genes & diseases 12 37692484
2023 Atorvastatin-mediated inhibition of prenylation of Rab27b and Rap1a in platelets attenuates their prothrombotic capacity and modulates clot structure. Platelets 11 37139869
2023 RAB27B Drives a Cancer Stem Cell Phenotype in NSCLC Cells Through Enhanced Extracellular Vesicle Secretion. Cancer research communications 10 37077938
2021 Silencing of long non-coding RNA SNHG15 suppresses proliferation, migration and invasion of pancreatic cancer cells by regulating the microRNA-345-5p/RAB27B axis. Experimental and therapeutic medicine 10 34594410
2020 Actions of Rab27B-GTPase on mammalian central excitatory synaptic transmission. Physiological reports 10 32358861
2025 Rab27b Promotes Lysosomal Function and Alpha-Synuclein Clearance in Neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 8 39965930
2022 RAB27B inhibits proliferation and promotes apoptosis of leukemic cells via 3-Hydroxy butyrate dehydrogenase 2 (BDH2). Bioengineered 8 35164665
2020 Rab27b contributes to radioresistance and exerts a paracrine effect via epiregulin in glioblastoma. Neuro-oncology advances 8 33409495
2012 Direct imaging of RAB27B-enriched secretory vesicle biogenesis in lacrimal acinar cells reveals origins on a nascent vesicle budding site. PloS one 8 22363735
2020 Inhibition of Rab27a and Rab27b Has Opposite Effects on the Regulation of Hair Cycle and Hair Growth. International journal of molecular sciences 7 32784729
2012 An immunohistochemical analysis of Rab27B distribution in fetal and adult tissue. The International journal of developmental biology 7 22811270
2023 Rab27b promotes endometriosis by enhancing invasiveness of ESCs and promoting angiogenesis. American journal of reproductive immunology (New York, N.Y. : 1989) 6 37641372
2021 Rab27b regulates extracellular vesicle production in cells infected with Kaposi's sarcoma-associated herpesvirus to promote cell survival and persistent infection. Journal of microbiology (Seoul, Korea) 6 33877577
2016 Genetic deletion of Rab27B in pancreatic acinar cells affects granules size and has inhibitory effects on amylase secretion. Biochemical and biophysical research communications 6 26845357
2012 Rab27b regulates c-kit expression by controlling the secretion of stem cell factor. Biochemical and biophysical research communications 6 22349512
2024 TGF-β regulates the release of breast cancer cell-derived extracellular vesicles and the sorting of their protein cargo by downregulating RAB27B expression. Journal of extracellular vesicles 5 39723610
2025 Mechanism of LINC01018/miR-182-5p/Rab27B in the immune escape through PD-L1-mediated CD8+ T cell suppression in glioma. Biology direct 4 40399992
2025 Rab27b-mediated CAFs derived exosomal miR-22-3p suppresses ferroptosis and promotes cisplatin resistance in osteosarcoma. Cellular signalling 4 40972800
2024 Tectoridin inhibits the growth of bladder cancer by regulating PI3K/MAPK pathway through RAB27B. Molecular carcinogenesis 4 38441297
2023 CaSR links endocytic and secretory pathways via MADD, a Rab11A effector that activates Rab27B. Cellular signalling 4 37604243
2024 Regulation of autophagy by Rab27B in colorectal cancer. The international journal of biochemistry & cell biology 3 39542128
2025 DDX10 Exacerbates Exosomal PD-L1-Dependent T Cell Exhaustion via Phase Separation of Rab27b in Oral Squamous Cell Carcinoma. Research (Washington, D.C.) 2 40352946
2020 Abnormal expression of Rab27B in prostatic epithelial cells of benign prostatic hyperplasia alters intercellular communication. The international journal of biochemistry & cell biology 2 33285290
2025 Microgravity-driven Rab27B activation amplifies mesenchymal stem cell-derived extracellular vesicle production and functions. Stem cell research & therapy 1 41163097
2024 Rab27b promotes lysosomal function and alpha-synuclein clearance in neurons. bioRxiv : the preprint server for biology 1 38979346
2026 Knockout of Rab27b exacerbates neuropathology in alpha-synuclein mouse models. Acta neuropathologica communications 0 42121002
2025 Positive feedback loop between NRASQ61R mutation and RAB27B expression in endothelial cells. Biochemical and biophysical research communications 0 39899936
2025 Lichong Decoction represses colorectal cancer progression via inhibiting the PINK1/Parkin pathway regulated by Rab27B. Journal of ethnopharmacology 0 40441460
2025 [Retracted] Silencing of long non-coding RNA SNHG15 suppresses proliferation, migration and invasion of pancreatic cancer cells by regulating the microRNA-345-5p/RAB27B axis. Experimental and therapeutic medicine 0 40692767
2025 Knockout of Rab27b exacerbates neuropathology in alpha-synuclein mouse models. bioRxiv : the preprint server for biology 0 41509326

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