Affinage

RAB32

Ras-related protein Rab-32 · UniProt Q13637

Length
225 aa
Mass
25.0 kDa
Annotated
2026-06-10
78 papers in source corpus 35 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAB32 is a dual-function small GTPase that couples canonical Rab membrane-trafficking activity to PKA signaling by acting as an A-kinase anchoring protein (AKAP) (PMID:12186851, PMID:17997311). It binds the type II regulatory subunit of PKA through determinants in its conserved alpha5 helix, tethering PKA to mitochondria, the ER/mitochondria-associated membrane (MAM), and melanosomes (PMID:12186851, PMID:17997311, PMID:20670942). As a GTPase it cycles between GTP- and GDP-bound states under the control of the BLOC-3 (HPS1–HPS4) GEF and its LYSMD1/2 co-activators, while RUTBC1 serves as its GAP (PMID:23084991, PMID:30837268, PMID:39078368, PMID:26620560); activity-dependent membrane recruitment in turn governs effector engagement. In its GTP-bound form RAB32 recruits effectors that execute distinct trafficking programs: VARP and Myosin Vc for delivery of Tyrp1 and other integral proteins to maturing melanosomes (PMID:19403694, PMID:25324551), and RTN3L for autophagic turnover of MAM-proximal ER proteins (PMID:34743744). Through this machinery RAB32 (acting partly redundantly with RAB38) directs TGN- and endosome-derived trafficking of melanogenic enzymes during melanosome biogenesis, recruiting ubiquitous adaptors including BLOC-2, AP-3 and AP-1, and assembling an LRMDA-Commander complex whose disruption underlies oculocutaneous albinism type 7 (PMID:17043139, PMID:22511774, PMID:41038817). At mitochondria and the MAM, PKA anchoring by RAB32 controls phosphorylation of Bad, Drp1 and PTPIP51 to modulate apoptotic timing, mitochondrial fission, and MERC integrity (PMID:12186851, PMID:20670942, PMID:42119358). RAB32 also constitutes a BLOC-3-dependent antimicrobial pathway that promotes phagosome maturation and restricts intracellular bacterial and fungal pathogens, a pathway actively subverted by pathogen effectors (PMID:23162001, PMID:31199852, PMID:33523895, PMID:39431830). Finally, RAB32 binds LRRK2 in a GTP-dependent manner via the LRRK2 armadillo domain to regulate its kinase activity, and the Parkinson's disease-associated Ser71Arg variant constitutively hyperactivates LRRK2 (PMID:31552791, PMID:38614108, PMID:38858457).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2002 High

    Established RAB32's defining non-canonical activity—that a Rab GTPase can act as an AKAP—answering how PKA is targeted to mitochondria and linking RAB32 to mitochondrial morphology.

    Evidence Yeast two-hybrid, co-fractionation and domain mapping of PKA-anchoring determinants; dominant-negative RAB32 expression with mitochondrial morphology readouts

    PMID:12186851

    Open questions at the time
    • Did not resolve whether AKAP and GTPase cycles are coupled
    • Mitochondrial fission role rested on overexpressed dominant-negative mutant
  2. 2002 Medium

    Defined the in vitro nucleotide-binding biochemistry of RAB32, revealing an atypical GTPase whose canonical Q85L 'GTPase-dead' substitution does not abolish hydrolysis.

    Evidence In vitro GTP-binding and GTPase assays with GST-fusion proteins and site-directed mutagenesis

    PMID:11784320

    Open questions at the time
    • No physiological GEF or GAP identified at this stage
    • Single-lab in vitro biochemistry
  3. 2006 High

    Placed RAB32 in melanosome biogenesis by showing it controls post-TGN trafficking of melanogenic enzymes, defining its best-characterized cellular role.

    Evidence siRNA knockdown of RAB32/RAB38, immunofluorescence, fractionation and pigmentation assays in melanocytes

    PMID:17043139

    Open questions at the time
    • Did not identify the effectors executing transport
    • Redundancy with RAB38 not yet resolved
  4. 2007 High

    Extended the AKAP function to melanosomes, showing RAB32 recruits PKA subunits to the melanosome surface in a GTP-dependent manner to regulate organelle transport.

    Evidence Co-IP, live-cell imaging and PKA/membrane-binding mutants in Xenopus melanophores

    PMID:17997311

    Open questions at the time
    • PKA substrates on melanosomes not defined
    • Heterologous melanophore system
  5. 2009 High

    Identified VARP as the first GTP-dependent effector and assigned RAB32 a specific cargo axis (Tyrp1) distinct from Pmel17, and linked active RAB32 to ER-based autophagy.

    Evidence Yeast two-hybrid with GTP-locked RAB32, deletion analysis and siRNA in melanocytes; gain/loss-of-function autophagy assays with LC3/p62 readouts

    PMID:19403694 PMID:19593531

    Open questions at the time
    • Mechanism linking VARP binding to vesicle delivery unresolved
    • Autophagy role from single lab, Medium confidence
  6. 2010 High

    Defined RAB32's role at the ER/mitochondria interface, showing PKA anchoring there controls Bad and Drp1 phosphorylation to set apoptotic timing and MAM composition.

    Evidence Subcellular fractionation, co-IP, ER calcium imaging and phospho-western blotting

    PMID:20670942

    Open questions at the time
    • Direct kinase–substrate relationships at MAM inferred from phosphorylation changes
    • Single lab
  7. 2011 High

    Identified RUTBC1 as a GAP that terminates RAB32 signaling, providing the off-switch of the GTPase cycle.

    Evidence In vitro GTPase activation assay with R803A mutagenesis and cellular co-IP showing altered VARP binding

    PMID:21808068

    Open questions at the time
    • Physiological setting of GAP action shown only later
    • Specificity among Rab targets partly overlapping with Rab33B
  8. 2012 High

    Identified BLOC-3 as the GEF that activates RAB32, connecting Hermansky-Pudlak syndrome genetics to RAB32 activation and membrane recruitment, and mapped additional trafficking adaptors and a megakaryocyte dense-granule role.

    Evidence GEF nucleotide-exchange assays, siRNA, membrane recruitment and pigmentation readouts; co-IP of BLOC-2/AP-3/AP-1; organelle tracing in MEG-01 cells

    PMID:22511774 PMID:22927249 PMID:23084991

    Open questions at the time
    • How BLOC-3 achieves membrane-specific recruitment not resolved
    • RAB32 vs RAB38 unique contributions only partly separated
  9. 2012 High

    Revealed a host-defense function: RAB32 and BLOC components form an antimicrobial pathway restricting Salmonella Typhi in macrophages.

    Evidence RNAi in macrophages with bacterial survival readouts and BLOC-deficient mouse macrophages

    PMID:23162001

    Open questions at the time
    • Molecular cargo delivered to restrict bacteria not defined here
    • Mechanism of restriction (acidification vs. toxic cargo) unresolved
  10. 2014 Medium

    Identified LRRK2 as a direct RAB32-family partner and added Myosin Vc and Drp1 as effectors, broadening RAB32 from trafficking into kinase regulation and mitochondrial dynamics.

    Evidence GFP-Trap co-IP (incl. endogenous LRRK2), yeast two-hybrid domain mapping, switch-II mutagenesis, comparative co-IP across the Rab32 family

    PMID:25324551 PMID:25360523 PMID:25767741

    Open questions at the time
    • Functional consequence of RAB32–LRRK2 binding not yet established
    • Drp1 interaction shown by co-IP without reconstitution
  11. 2015 High

    Confirmed RUTBC1 as the physiological GAP in melanocytes, showing bidirectional disruption of the GTPase cycle impairs trafficking of all three melanogenic enzymes.

    Evidence siRNA, GAP activity assay and immunofluorescence for melanogenic enzymes in melan-a cells

    PMID:26620560

    Open questions at the time
    • Spatiotemporal coordination of GEF and GAP not fully defined
    • Single lab
  12. 2019 High

    Provided structural and mechanistic detail of the GTP-dependent RAB32–LRRK2 interface and refined BLOC-3 GEF requirements, separating GEF activity from Rab9 binding in melanogenesis; also linked RAB32 to retromer/SNX6, phagosome maturation, and dense-organelle trafficking.

    Evidence X-ray crystallography and ARM-domain/switch-1 mutagenesis; HPS4 separation-of-function rescue; co-IP with SNX6; RNAi phagosome acidification and cathepsin D assays

    PMID:30640902 PMID:30837268 PMID:31199852 PMID:31552791

    Open questions at the time
    • Whether structural interface dictates LRRK2 kinase output not yet tested
    • SNX6 link rests on single-lab co-IP
  13. 2020 Medium

    Connected RAB32 to lysosomal mTORC1 signaling, showing it supports mTOR recruitment and restrains TFEB-driven lysosome biogenesis.

    Evidence Co-IP with mTOR, siRNA, mTORC1 signaling and TFEB localization readouts

    PMID:32295849

    Open questions at the time
    • Whether RAB32 directly scaffolds mTORC1 or acts indirectly unresolved
    • Single lab
  14. 2021 High

    Generalized the antimicrobial pathway across pathogens and host species and identified the RTN3L effector arm of RAB32-driven MAM-phagy.

    Evidence Knockdown across human/murine macrophages with bacterial/fungal killing and SPI-1 mutants; co-IP and organellar degradation assays for RTN3L/TMX1

    PMID:33523895 PMID:34743744

    Open questions at the time
    • How RAB32 selects MAM-phagy cargo not defined
    • RTN3L data Medium confidence, single lab
  15. 2024 Medium

    Provided the mechanistic basis for RAB32 in Parkinson's disease, showing the Ser71Arg variant hyperactivates LRRK2 kinase, and identified LYSMD1/2 as BLOC-3 co-activators of RAB32.

    Evidence Cell-based LRRK2 S1292 autophosphorylation assays comparing WT vs S71R (two independent studies); co-IP and CRISPR knockout of LYSMD1/2 with melanin/melanosome readouts; BopE T3SS effector interference assay

    PMID:38614108 PMID:38858457 PMID:39078368 PMID:39431830

    Open questions at the time
    • Whether S71R alters RAB32's own trafficking functions not established
    • Tissue context of LRRK2 hyperactivation in neurons not directly tested
  16. 2025 High

    Resolved RAB32's role in melanosome biogenesis disease and in PKA-dependent Golgi organization, and extended its functions into autophagosomal recycling and immune cross-priming.

    Evidence Proteomics/reconstitution defining RAB32–LRMDA–Commander (OCA7); RAB32–OPTN co-IP with PKA phosphorylation and Golgi/migration rescue; recycler-complex assays; Rab32-KO mouse cross-priming and tumor models (preprint)

    PMID:38323995 PMID:40258145 PMID:41038817 PMID:bio_10.1101_2025.05.03.652057

    Open questions at the time
    • Cross-priming role is a preprint not yet peer-reviewed
    • How AKAP-driven OPTN phosphorylation integrates with Golgi-resident RAB32 unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how RAB32's distinct effector and AKAP outputs are coordinated across organelles, and whether disease-causing variants act primarily through LRRK2 hyperactivation, altered trafficking, or both.
  • No structural model integrating GTPase cycle with AKAP function
  • Causal hierarchy among LRRK2, melanosome, and antimicrobial roles in disease undefined
  • In vivo physiological consequences of S71R hyperactivation not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005739 mitochondrion 6 GO:0031410 cytoplasmic vesicle 4 GO:0005764 lysosome 3 GO:0005768 endosome 3 GO:0005783 endoplasmic reticulum 3 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-9609507 Protein localization 4 R-HSA-168256 Immune System 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9612973 Autophagy 3
Partners
DRP1LRMDALRRK2MYO5COPTNPRKAR2RTN3VARP

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 RAB32 functions as an A-kinase anchoring protein (AKAP) by directly interacting with the type II regulatory subunit (RII) of PKA via determinants within the conserved alpha5 helix common to all Rab family members, thereby tethering PKA to mitochondria. Yeast two-hybrid, cellular co-fractionation, immunofluorescence, biochemical mapping of PKA-anchoring determinants The Journal of cell biology High 12186851
2002 Expression of a GTP-binding-deficient mutant of RAB32 promotes aberrant perinuclear accumulation of mitochondria and disruption of the microtubule cytoskeleton results in aberrantly elongated mitochondria, implicating RAB32 in mitochondrial fission. Transient transfection of dominant-negative RAB32 mutant, immunofluorescence, microtubule disruption assays The Journal of cell biology Medium 12186851
2002 RAB32 and RAB31, expressed as GST-fusion proteins, bind GTP (measured as [35S]GTPγS) in a Mg2+-dependent manner and display low intrinsic GTPase activity; notably, the Q85L GTPase-dead mutation does not abolish GTPase activity as it does in most Rab proteins. In vitro GTP-binding and GTPase activity assays using GST-fusion proteins; site-directed mutagenesis (Q85L) European journal of biochemistry Medium 11784320
2006 RAB32 and RAB38 co-localize to perinuclear vesicles carrying tyrosinase and tyrosinase-related protein 1 (Tyrp1), and in cells deficient for both RAB38 and RAB32 (via siRNA knockdown), tyrosinase is mistargeted and degraded after exit from the trans-Golgi network, demonstrating that RAB32 regulates TGN-to-melanosome trafficking of melanogenic enzymes. siRNA knockdown, immunofluorescence, subcellular fractionation, pigmentation assay in cht melanocytes The Journal of cell biology High 17043139
2007 In Xenopus melanophores, RAB32 localizes to the melanosome surface in a GTP-dependent manner and recruits both RIIα and Cβ subunits of PKA to melanosomes, functioning as a melanosome-specific AKAP essential for PKA-mediated regulation of melanosome transport. Co-immunoprecipitation, live-cell imaging, overexpression of wild-type and PKA-binding or melanosome-binding mutants, melanosome aggregation assay Current biology : CB High 17997311
2009 RAB32 localizes to the ER in its GTP-bound (active) form; overexpression induces formation of autophagic vacuoles containing LC3, calnexin and LAMP-2 even under nutrient-rich conditions, and ER membrane recruitment is required for this activity. Conversely, inactive RAB32 or siRNA knockdown prevents constitutive autophagy and causes accumulation of p62/SQSTM1-positive aggresome-like structures. Transient transfection of wild-type and mutant RAB32, immunofluorescence for LC3/calnexin/LAMP-2, siRNA knockdown, p62/ubiquitin staining Cellular and molecular life sciences : CMLS Medium 19593531
2009 VARP/Ankrd27 is a GTP-dependent effector of RAB32 and RAB38; its first ankyrin-repeat domain (ANKR1) binds active (GTP-locked) RAB32/38, and siRNA knockdown of VARP or expression of the ANKR1 domain causes dramatic loss of Tyrp1 from melanosomes without affecting Pmel17, establishing RAB32 → VARP as a specific axis for Tyrp1 trafficking. Yeast two-hybrid screening with GTP-locked RAB32/38, deletion analysis, siRNA knockdown, immunofluorescence in melan-a cells Molecular biology of the cell High 19403694
2010 RAB32 localizes to the ER and mitochondria and regulates MAM properties: RAB32 modulates ER calcium handling, disrupts specific enrichment of calnexin on the MAM (without affecting PDI or mitofusin-2), and determines PKA targeting to mitochondrial and ER membranes. Through PKA anchoring, RAB32 overexpression or inactivation increases phosphorylation of Bad and Drp1, thereby modulating the speed of apoptosis onset. Subcellular fractionation, co-immunoprecipitation, ER calcium measurements, immunofluorescence, phospho-western blotting for Bad/Drp1 The Journal of biological chemistry High 20670942
2011 RUTBC1, a TBC-domain (GAP) protein, is a Rab9A effector that activates GTP hydrolysis specifically by RAB32 and Rab33B in vitro; catalysis requires Arg-803 of RUTBC1. In cells, RUTBC1 influences the ability of RAB32 to bind its effector VARP, indicating physiological regulation of RAB32 activity. In vitro GTPase activation assay, site-directed mutagenesis (R803A), co-immunoprecipitation, GTP-hydrolysis biochemical screening The Journal of biological chemistry High 21808068
2012 BLOC-3 (HPS1–HPS4 complex), mutated in Hermansky-Pudlak syndrome, functions as a guanine nucleotide exchange factor (GEF) for RAB32 and RAB38; BLOC-3 promotes specific membrane recruitment of RAB32/38, and silencing of HPS1 or HPS4 mislocalizes RAB32/38 and reduces pigmentation. GEF activity assay (nucleotide exchange), siRNA knockdown, co-immunoprecipitation, membrane recruitment assay, pigmentation readout Current biology : CB High 23084991
2012 BLOC-2, AP-3, and AP-1 co-immunoprecipitate with RAB32 and RAB38 from melanocytic cell extracts and partially co-localize with them; RAB32/RAB38-deficient cells show abnormal trafficking of tyrosinase and Tyrp1, demonstrating that RAB32 directs ubiquitous trafficking machinery to mediate transport from early endosomes to maturing melanosomes. RAB32 has unique functions in melanosome biogenesis that cannot be replaced by RAB38. Co-immunoprecipitation from MNT-1 cells, siRNA knockdown of Rab32/38, confocal immunofluorescence, western blotting The Journal of biological chemistry High 22511774
2012 RAB32 and RAB38 are required for vesicle fusion delivering dense granule cargo to maturing dense granules in megakaryocytic cells; sorting signals recognized by adaptor protein-3 are necessary for normal transport to dense granules. Endocytic tracing with dextran, mepacrine staining, co-localization studies, mutant dense-granule protein mis-targeting experiments in MEG-01 cells Blood Medium 22927249
2012 A Rab32-dependent pathway controls Salmonella Typhi host restriction: RNAi-mediated depletion of RAB32 or of a BLOC complex component allows S. Typhi to survive within mouse macrophages, demonstrating that RAB32 and BLOC components are essential for an antimicrobial trafficking pathway. RNA interference in macrophages, bacterial survival assay, macrophages from BLOC-deficient mice Science (New York, N.Y.) High 23162001
2014 RAB32 and RAB38 (but no other tested GTPases) directly interact with LRRK2; the interaction domain maps to a predicted coiled-coil region in the LRRK2 N-terminus. RAB32 co-localizes with LRRK2 at recycling endosomes, and constitutively active RAB32 increases co-localization with Rab7/9-positive late endosomes/MVBs. Subcellular fractionation supports RAB32's role in LRRK2 late endosomal transport. GFP-Trap co-immunoprecipitation (including endogenous LRRK2), yeast two-hybrid domain mapping, fluorescence microscopy, subcellular fractionation PloS one Medium 25360523
2014 Myosin Vc is an effector of RAB32 and RAB38 in melanosomes; it was isolated by yeast two-hybrid screening and binding depends on residues in the switch II region of RAB32/38 and regions of the Myosin Vc coiled-coil tail. Knockdown of Myosin Vc causes trafficking defects of integral membrane proteins to melanosomes. Yeast two-hybrid screening, co-immunoprecipitation, domain-level mutagenesis (switch II), siRNA knockdown with cargo readout in MNT-1 cells The Journal of biological chemistry High 25324551
2014 RAB32 interacts with Drp1 (dynamin-related protein 1); this interaction is evolutionarily conserved among the Rab32 subfamily including paralogs Rab32A, Rab32B, Rab29, and Rab38. The extent of ER association of Rab32 family proteins dictates their mitochondrial function. Co-immunoprecipitation, evolutionary/comparative cell biology analyses across Rab32 family members Cellular logistics Medium 25767741
2015 RUTBC1 functions as a physiological GAP for RAB32/38 in melanocytes; either excess activation (RUTBC1 knockdown) or inactivation (RUTBC1 overexpression) of RAB32/38 impairs trafficking of all three melanogenic enzymes (tyrosinase, Tyrp1, dopachrome tautomerase). Rab9A binding regulates RUTBC1 localization and thus the spatiotemporal control of RAB32/38 activity. siRNA knockdown of RUTBC1, GAP activity assay, immunofluorescence for melanogenic enzymes in melan-a cells The Journal of biological chemistry High 26620560
2019 LRRK2 binds the RAB32 subfamily in a GTP-dependent manner via its armadillo (ARM) domain; crystal structures of Rab32-family GTPases reveal a positively charged residue in switch 1 critical for LRRK2 binding, and mutational analysis of the LRRK2 ARM domain identifies negatively charged residues contributing to complex formation. X-ray crystallography of RAB32-family GTPases, in vitro biochemical binding assay with purified proteins, site-directed mutagenesis of switch 1 (RAB32/38) and ARM domain (LRRK2), homology modelling Small GTPases High 31552791
2019 The HPS4 subunit of BLOC-3 is required for Rab32/38-GEF activity in melanogenesis; an HPS4 mutant lacking Rab32/38-GEF activity fails to rescue tyrosinase trafficking or melanin content in HPS4-deficient melanocytes, whereas a Rab9-binding-deficient HPS4 mutant fully rescues the phenotype, demonstrating that BLOC-3's GEF activity toward RAB32 is essential and Rab9 binding is dispensable for melanogenesis. Site-directed mutagenesis of HPS4 (GEF-activity and Rab9-binding mutants), rescue experiments in melan-le cells, tyrosinase trafficking and melanin content assays The Journal of biological chemistry High 30837268
2019 RAB32 directly interacts with sorting nexin 6 (SNX6), a retromer subunit; both RAB32 and SNX6 affect the localization of cation-independent mannose-6-phosphate receptors (CI-MPRs) recycled by the retromer to the trans-Golgi network. Co-immunoprecipitation (RAB32–SNX6), confocal immunofluorescence for CI-MPR localization, knockdown experiments PloS one Medium 30640902
2019 RAB32 promotes phagosome maturation during Burkholderia pseudomallei infection: RAB32 enhances phagosome acidification and fusion of bacterial phagosomes with lysosomes to activate cathepsin D, restricting intracellular bacterial growth. This activity depends on RAB32's GTP/GDP binding state. RNAi knockdown, phagosome acidification assay, cathepsin D activation assay, bacterial survival/growth assay, live imaging of RAB32-positive compartments PLoS pathogens Medium 31199852
2020 RAB32 associates with lysosomes and supports mTORC1 signaling; RAB32 interacts with mTOR kinase, and RAB32 depletion reduces association of mTOR and mTORC1 pathway components with lysosomes, increases nuclear TFEB localization, and promotes lysosome biogenesis. Co-immunoprecipitation (RAB32–mTOR), siRNA knockdown, mTORC1 signaling readouts (p-S6K, p-4EBP1), TFEB nuclear localization assay, subcellular fractionation Journal of cell science Medium 32295849
2021 The RAB32/BLOC-3 antimicrobial pathway is active in both human and murine macrophages against bacterial and fungal pathogens, independent of NADPH oxidase, nitric oxide, and antimicrobial peptides. S. Typhi actively counteracts this pathway via its SPI-1 type III secretion system to survive in human macrophages. Genetic knockdown (siRNA/shRNA) of RAB32 and BLOC-3 subunits, bacterial/fungal survival assays, inhibitor studies ruling out alternative mechanisms, SPI-1 mutant bacteria Science advances High 33523895
2021 RAB32 uses the long isoform of reticulon-3 (RTN3L) as an effector to promote autophagic degradation (MAM-phagy) of mitochondria-proximal ER membrane proteins, including TMX1; RTN3L was identified as a RAB32-binding effector distinct from Drp1. Co-immunoprecipitation (RAB32–RTN3L), organellar protein degradation assay, loss-of-function (RAB32 depletion), panel of MERC protein substrates tested Biology direct Medium 34743744
2024 The RAB32 Ser71Arg variant activates LRRK2 kinase activity to a significantly greater degree than wild-type RAB32 Ser71 in transfected cells, providing a mechanistic link between this PD-associated variant and the LRRK2 kinase pathway. In vitro transfection assay measuring LRRK2 autophosphorylation (S1292) as readout of LRRK2 kinase activity; wild-type vs. Ser71Arg comparison The Lancet. Neurology Medium 38614108 38858457
2024 RAB32 S71R increases LRRK2 kinase activity as measured by increased LRRK2 autophosphorylation at S1292, independently confirming that mutant RAB32 activates LRRK2 kinase. Functional in vitro kinase assay (LRRK2 S1292 autophosphorylation) comparing RAB32 WT vs. S71R Nature genetics Medium 38858457
2024 LYSMD1 and LYSMD2 physically interact with the HPS1 subunit of BLOC-3 (RAB32/38 GEF) to promote RAB32 activation; inactivation of both LYSMD1 and LYSMD2 reduces RAB32 activation, causing melanosome enlargement and decreased melanin production. Co-immunoprecipitation (LYSMD–HPS1), RAB32 activation assay, CRISPR knockout of LYSMD1/2 in mouse melanoma cells, melanin production assay, melanosome morphology The Journal of cell biology Medium 39078368
2024 Rab32 family proteins (RAB32 and RAB7L1/Rab29) localize to autolysosomes and are required for autophagosomal component recycling (ACR) through the recycler complex (SNX4/5/17); the GTPase cycle of Rab32 family proteins (governed by their GEF and GAP) regulates recycler complex formation and connection between recycler-cargo and the dynactin complex. Loss-of-function knockdown/knockout of Rab32 family members, co-localization with autolysosome markers, recycler complex assembly assay, dynactin interaction assay The Journal of cell biology Medium 38323995
2025 RAB32 directly interacts with LRMDA (leucine-rich melanocyte differentiation associated protein), which simultaneously associates with the Commander endosomal trafficking complex. RAB32, LRMDA, and Commander form a distinct assembly (separate from SNX17-Commander) required for melanosome biogenesis; LRMDA mutations causing oculocutaneous albinism type 7 uncouple RAB32 and Commander binding. Unbiased proteomics, recombinant protein reconstitution, co-immunoprecipitation, computational modelling, functional analysis in human melanocytes (knockdown/rescue), melanosome morphology and pigmentation assay Nature communications High 41038817
2025 RAB32 AKAP function is required for Golgi organization: Rab32 directly interacts with optineurin (OPTN) and facilitates PKA-dependent phosphorylation of OPTN at Ser342. Blocking OPTN Ser342 phosphorylation causes Golgi fragmentation, and a phospho-mimetic OPTN rescues Golgi defects induced by PKA-binding-deficient RAB32 (L188P). RAB32 AKAP function and OPTN phosphorylation are required for Golgi repositioning and directional cell migration. Co-immunoprecipitation (RAB32–OPTN), site-directed mutagenesis (RAB32 L188P, OPTN S342A, S342E), PKA phosphorylation assay, live-cell Golgi imaging, cell migration assay, rescue experiments Proceedings of the National Academy of Sciences of the United States of America High 40258145
2025 RAB32 is required for efficient in vivo cross-priming of CD8+ T cells against cell-associated antigens by XCR1+ type 1 dendritic cells (cDC1s); RAB32-deficient cDC1s develop normally but fail to support effective antigen-specific CD8+ T cell expansion in vivo, and RAB32-mediated cross-priming is required for tumor-specific CD8+ T cell infiltration into solid tumors. Rab32 knockout mice, in vivo cross-priming assay with cell-associated antigen, ex vivo T cell stimulation, tumor model bioRxivpreprint Medium bio_10.1101_2025.05.03.652057
2026 RAB32 promotes mitochondria-associated membrane (MERC) integrity in hepatocellular carcinoma cells by promoting mitochondrial PKA localization, which facilitates PKA-dependent phosphorylation of PTPIP51, maintaining MERCs and mitochondrial Ca2+ homeostasis. Co-immunoprecipitation, subcellular fractionation, mitochondrial Ca2+ measurement, synthetic MERC linker rescue, siRNA knockdown of RAB32 Pathology, research and practice Medium 42119358
2017 HCV infection converts GTP-bound RAB32 to GDP-bound RAB32, causing RAB32 aggregation; GDP-bound RAB32 selectively interacts with HCV core protein and deposits it into ER-associated perinuclear aggregates that function as viral assembly sites. RAB32 is required specifically for HCV virion assembly but not other stages of the HCV life cycle. Co-immunoprecipitation (RAB32–HCV core), siRNA knockdown with defined stage-specific viral replication assay, immunofluorescence Journal of virology Medium 27852857
2025 Peripheral inflammation (LPS) selectively induces RAB32 expression in midbrain Iba1+ microglia (but not dopaminergic neurons), where it localizes to Lamp1+ lysosomes and correlates with Lrrk2 kinase activity. Tfe3 (a lysosomal biogenesis transcription factor) translocates to the nucleus of inflamed microglia to drive RAB32 expression and downstream LRRK2 activation; Tfe3 knockdown, but not Tfeb knockdown, mitigates these effects. LPS in vivo and in vitro (iPSC-microglia) treatment, immunofluorescence, kinase activity assay, Tfe3/Tfeb shRNA knockdown, promoter analysis bioRxivpreprint Medium 41846967
2025 RAB32 anchors FANCD2 to mitochondria in cardiomyocytes; RAB32 downregulation decreases mitochondrial FANCD2 protein levels, and FANCD2 knockdown reverses the protective effect of RAB32 on OGD/R-induced cardiomyocyte injury. Co-immunoprecipitation (RAB32–FANCD2), subcellular fractionation showing mitochondrial FANCD2 localization, siRNA knockdown, OGD/R injury model International immunopharmacology Low 40286784
2024 BopE, a B. pseudomallei T3SS effector, directly interacts with host RAB32 and suppresses RAB32 activation by interfering with nucleotide exchange, thereby reducing Rab32 recruitment to bacterial-containing vesicles and promoting bacterial intracellular survival. Co-immunoprecipitation (BopE–RAB32), nucleotide exchange interference assay, bopE knockout bacteria with Rab32-positive vesicle quantification and survival assay mSphere Medium 39431830

Source papers

Stage 0 corpus · 78 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Rab38 and Rab32 control post-Golgi trafficking of melanogenic enzymes. The Journal of cell biology 241 17043139
2012 BLOC-3 mutated in Hermansky-Pudlak syndrome is a Rab32/38 guanine nucleotide exchange factor. Current biology : CB 231 23084991
2002 Rab32 is an A-kinase anchoring protein and participates in mitochondrial dynamics. The Journal of cell biology 197 12186851
2010 Rab32 modulates apoptosis onset and mitochondria-associated membrane (MAM) properties. The Journal of biological chemistry 148 20670942
2011 Identification of two new loci at IL23R and RAB32 that influence susceptibility to leprosy. Nature genetics 139 22019778
2012 A Rab32-dependent pathway contributes to Salmonella typhi host restriction. Science (New York, N.Y.) 135 23162001
2012 BLOC-2, AP-3, and AP-1 proteins function in concert with Rab38 and Rab32 proteins to mediate protein trafficking to lysosome-related organelles. The Journal of biological chemistry 112 22511774
2009 A small GTPase, human Rab32, is required for the formation of autophagic vacuoles under basal conditions. Cellular and molecular life sciences : CMLS 98 19593531
2009 Varp is a novel Rab32/38-binding protein that regulates Tyrp1 trafficking in melanocytes. Molecular biology of the cell 96 19403694
2024 RAB32 Ser71Arg in autosomal dominant Parkinson's disease: linkage, association, and functional analyses. The Lancet. Neurology 91 38614108
2012 Rab32 is important for autophagy and lipid storage in Drosophila. PloS one 90 22348149
2012 Mechanism of platelet dense granule biogenesis: study of cargo transport and function of Rab32 and Rab38 in a model system. Blood 86 22927249
2014 LRRK2 transport is regulated by its novel interacting partner Rab32. PloS one 83 25360523
2017 Rab32 connects ER stress to mitochondrial defects in multiple sclerosis. Journal of neuroinflammation 63 28115010
2019 LRRK2 binds to the Rab32 subfamily in a GTP-dependent manner via its armadillo domain. Small GTPases 59 31552791
2024 Systematic rare variant analyses identify RAB32 as a susceptibility gene for familial Parkinson's disease. Nature genetics 58 38858457
2014 Myosin vc interacts with Rab32 and Rab38 proteins and works in the biogenesis and secretion of melanosomes. The Journal of biological chemistry 58 25324551
2012 Cell type-specific Rab32 and Rab38 cooperate with the ubiquitous lysosome biogenesis machinery to synthesize specialized lysosome-related organelles. Small GTPases 53 23247405
2011 RUTBC1 protein, a Rab9A effector that activates GTP hydrolysis by Rab32 and Rab33B proteins. The Journal of biological chemistry 53 21808068
2002 Molecular cloning, bacterial expression and properties of Rab31 and Rab32. European journal of biochemistry 46 11784320
2023 Rab32 promotes glioblastoma migration and invasion via regulation of ERK/Drp1-mediated mitochondrial fission. Cell death & disease 43 36922509
2006 RAB32 hypermethylation and microsatellite instability in gastric and endometrial adenocarcinomas. International journal of cancer 39 16557577
2007 Rab32 regulates melanosome transport in Xenopus melanophores by protein kinase a recruitment. Current biology : CB 38 17997311
2015 RUTBC1 Functions as a GTPase-activating Protein for Rab32/38 and Regulates Melanogenic Enzyme Trafficking in Melanocytes. The Journal of biological chemistry 36 26620560
2014 Interaction with the effector dynamin-related protein 1 (Drp1) is an ancient function of Rab32 subfamily proteins. Cellular logistics 35 25767741
2020 The small GTPase Rab32 resides on lysosomes to regulate mTORC1 signaling. Journal of cell science 34 32295849
2019 Rab32 GTPase, as a direct target of miR-30b/c, controls the intracellular survival of Burkholderia pseudomallei by regulating phagosome maturation. PLoS pathogens 34 31199852
2018 Function and regulation of the Caenorhabditis elegans Rab32 family member GLO-1 in lysosome-related organelle biogenesis. PLoS genetics 32 30419011
2011 The Rab21-GEF activity of Varp, but not its Rab32/38 effector function, is required for dendrite formation in melanocytes. Molecular biology of the cell 30 22171327
2021 The Rab32/BLOC-3-dependent pathway mediates host defense against different pathogens in human macrophages. Science advances 29 33523895
2019 The BLOC-3 subunit HPS4 is required for activation of Rab32/38 GTPases in melanogenesis, but its Rab9 activity is dispensable for melanogenesis. The Journal of biological chemistry 27 30837268
2016 Rab32 restriction of intracellular bacterial pathogens. Small GTPases 27 27645564
2012 Expression profiling of Rab GTPases reveals the involvement of Rab20 and Rab32 in acute brain inflammation in mice. Neuroscience letters 26 22960262
2015 Rab32 is essential for maintaining functional acidocalcisomes, and for growth and infectivity of Trypanosoma cruzi. Journal of cell science 25 25964650
2021 Rab32 uses its effector reticulon 3L to trigger autophagic degradation of mitochondria-associated membrane (MAM) proteins. Biology direct 24 34743744
2016 Depletion of Rab32 decreases intracellular lipid accumulation and induces lipolysis through enhancing ATGL expression in hepatocytes. Biochemical and biophysical research communications 23 26882978
2019 Combined deficiency of RAB32 and RAB38 in the mouse mimics Hermansky-Pudlak syndrome and critically impairs thrombosis. Blood advances 22 31399401
2024 Rab32 facilitates Schwann cell pyroptosis in rats following peripheral nerve injury by elevating ROS levels. Journal of translational medicine 21 38388913
2019 Rab32 interacts with SNX6 and affects retromer-dependent Golgi trafficking. PloS one 20 30640902
2020 MicroRNA-141-5p Acts as a Tumor Suppressor via Targeting RAB32 in Chronic Myeloid Leukemia. Frontiers in pharmacology 19 32038235
2016 Rab32 and Rab38 genes in chordate pigmentation: an evolutionary perspective. BMC evolutionary biology 18 26818140
2021 Reduced expression of miR-30c-5p promotes hepatocellular carcinoma progression by targeting RAB32. Molecular therapy. Nucleic acids 16 34703646
2024 Rab32 family proteins regulate autophagosomal components recycling. The Journal of cell biology 15 38323995
2023 Characterization of Rab32- and Rab38-positive lysosome-related organelles in osteoclasts and macrophages. The Journal of biological chemistry 15 37625588
2017 Hepatitis C Virus-Induced Rab32 Aggregation and Its Implications for Virion Assembly. Journal of virology 15 27852857
2015 Improvement in Mouse iPSC Induction by Rab32 Reveals the Importance of Lipid Metabolism during Reprogramming. Scientific reports 15 26559473
2022 Ras-Related Protein Rab-32 and Thrombospondin 1 Confer Resistance to the EGFR Tyrosine Kinase Inhibitor Osimertinib by Activating Focal Adhesion Kinase in Non-Small Cell Lung Cancer. Cancers 12 35884490
2010 Rab32 and the remodeling of the imaginal midgut in Helicoverpa armigera. Amino acids 12 20960213
2022 MicroRNA-30 inhibits the growth of human ovarian cancer cells by suppressing RAB32 expression. International journal of immunopathology and pharmacology 11 34986662
2024 The RAB32 p.Ser71Arg Variant in Parkinsonisms: Insights from a Large Italian Cohort. Movement disorders : official journal of the Movement Disorder Society 9 39737595
2022 The hsa_circ_0039857/miR-338-3p/RAB32 axis promotes the malignant progression of colorectal cancer. BMC gastroenterology 9 36539702
2023 Rab32 and Rab38 maintain bone homeostasis by regulating intracellular traffic in osteoclasts. Cell structure and function 8 37793839
2018 Rab32-related antimicrobial pathway is involved in the progression of dextran sodium sulfate-induced colitis. FEBS open bio 8 30338217
2024 A pathogenic variant in RAB32 causes autosomal dominant Parkinson's disease and activates LRRK2 kinase. medRxiv : the preprint server for health sciences 7 38293014
2020 VARP and Rab9 Are Dispensable for the Rab32/BLOC-3 Dependent Salmonella Killing. Frontiers in cellular and infection microbiology 7 33392103
2018 Transcriptional regulation of Rab32/38, a specific marker of pigment cell formation in Ciona robusta. Developmental biology 7 30471267
2012 Organelle biogenesis: en BLOC exchange for RAB32 and RAB38. Current biology : CB 7 23174301
2018 Expression of a T39N mutant Rab32 protein arrests mitochondria movement within neurites of differentiated SH-SY5Y cells. Small GTPases 6 29261068
2022 Rab32/38-Dependent and -Independent Transport of Tyrosinase to Melanosomes in B16-F1 Melanoma Cells. International journal of molecular sciences 5 36430618
2024 LYSMD proteins promote activation of Rab32-family GTPases for lysosome-related organelle biogenesis. The Journal of cell biology 4 39078368
2025 18F-FDG PET findings in Parkinson's disease associated to RAB32 S71R variant. Parkinsonism & related disorders 3 40117893
2025 Identification of Ser71Arg mutation in RAB32 gene in familial Parkinson's disease from Southern Italy. NPJ Parkinson's disease 3 40118982
2025 Rab32 regulates Golgi structure and cell migration through Protein Kinase A-mediated phosphorylation of Optineurin. Proceedings of the National Academy of Sciences of the United States of America 3 40258145
2024 The host Rab9a/Rab32 axis is actively recruited to the Trypanosoma cruzi parasitophorous vacuole and benefits the infection cycle. Molecular microbiology 3 38193389
2024 RAB32 promotes glioma cell progression by activating the JAK/STAT3 signaling pathway. The Journal of international medical research 3 39628429
2024 High Expression of RAB32 Predicts Adverse Outcomes: A Potential Therapeutic Target for Glioblastoma. Journal of Cancer 3 39668831
2023 Rab32, a novel Rab small GTPase from orange-spotted grouper, Epinephelus coioides involved in SGIV infection. Fish & shellfish immunology 2 37972745
2026 Peripheral inflammation mediates midbrain Lrrk2 kinase activity via Rab32 expression. bioRxiv : the preprint server for biology 1 41846967
2025 Rab32-based vesicles coordinate mitochondria and actin for spindle migration and organelle rearrangement in oocyte meiosis. Journal of advanced research 1 40324632
2025 The Rab32-LRMDA-Retriever Complex is a Key Regulator of Intestinal Immune Homeostasis. bioRxiv : the preprint server for biology 1 40791432
2025 Identification of a RAB32-LRMDA-Commander membrane trafficking complex reveals the molecular mechanism of human oculocutaneous albinism type 7. Nature communications 1 41038817
2024 Deciphering the molecular regulatory of RAB32/GPRC5A axis in chronic obstructive pulmonary disease. Respiratory research 1 38448858
2024 Burkholderia pseudomallei BopE suppresses the Rab32-dependent defense pathway to promote its intracellular replication and virulence. mSphere 1 39431830
2026 Targeting UGCG sensitizes AML cells to venetoclax through RAB32-mediated endoplasmic reticulum-mitochondria communication. Cell reports 0 41734065
2026 Rab32-mediated macrophage apoptosis and apoptotic body release promote M1 polarization in ARDS via the Cxcl11/Ccl4/NF-κB pathway. International immunopharmacology 0 41763169
2026 Reduced mitochondrial Rab32 impairs mitochondria-endoplasmic reticulum contacts and inhibits apoptosis in hepatocellular carcinoma cells. Pathology, research and practice 0 42119358
2025 Identification of a RAB32-LRMDA-Commander membrane trafficking complex reveals the molecular mechanism of human oculocutaneous albinism type 7. bioRxiv : the preprint server for biology 0 39975051
2025 Rab32 protects mitochondrial function by anchoring Fancd2 and mediates the protective effect of penehyclidine hydrochloride against myocardial ischemia-reperfusion injury. International immunopharmacology 0 40286784

Missed literature

Know a paper Affinage missed for RAB32? Flag it for the maintainers and the community.

No submissions yet.