Affinage

RAB4A

Ras-related protein Rab-4A · UniProt P20338

Length
218 aa
Mass
24.4 kDa
Annotated
2026-04-28
100 papers in source corpus 58 papers cited in narrative 58 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAB4A is a small GTPase that functions as a master regulator of rapid recycling and sorting at early/sorting endosomes, directing the return of diverse transmembrane cargoes—including transferrin receptor, integrins αvβ3 and α5β1, GLUT4, β-adrenergic receptors, AMPA receptors, CD4, TCRζ, and SERT—to the plasma membrane, while also controlling cargo routing to lysosomes and autophagosome formation (PMID:1516131, PMID:11566097, PMID:8943343, PMID:16935861, PMID:24404161). RAB4A organizes distinct membrane microdomains on early endosomes together with Rab5 and Rab11, orchestrates a downstream GTPase cascade (Arl1→BIG1/2→Arf1) that recruits AP-1/AP-3/GGA coat complexes, and engages effectors including Rabaptin-5, RCP, GRASP-1, NDRG1, and the motor proteins KIF3 and dynein LIC-1 to achieve cargo segregation and vesicle transport (PMID:10811830, PMID:24835460, PMID:12832475, PMID:20098723, PMID:30154210). Its GTP/GDP cycling is regulated by PI3K-dependent GEF activity, p34cdc2/ERK1 phosphorylation at Ser196, GDI-mediated membrane–cytosol shuttling, ICMT-catalyzed carboxylmethylation, serotonylation, and the GAP TBC1D16 (PMID:9169411, PMID:1425574, PMID:28604748, PMID:18227069, PMID:23019362). In T cells, constitutively active RAB4A drives CD98 recycling and mTOR activation, promoting autoimmune pathology in lupus-prone mice, while RAB4A deletion attenuates glomerulonephritis (PMID:38519468).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1991 High

    Establishing where RAB4A resides resolved the first mechanistic question—which trafficking compartment it might regulate—by demonstrating tight association with early endosomes containing transferrin receptor.

    Evidence Subcellular fractionation (free-flow electrophoresis, Percoll gradients) and immunofluorescence in cultured cells

    PMID:1906178

    Open questions at the time
    • No functional consequence of localization established
    • No distinction between sorting and recycling endosomes
  2. 1992 High

    The functional role of RAB4A was defined: overexpression redistributed transferrin receptors to the plasma membrane and blocked iron discharge, establishing RAB4A as a positive regulator of early endosomal recycling, while mitotic phosphorylation at Ser196 by p34cdc2 provided the first regulatory mechanism controlling its membrane association.

    Evidence Stable overexpression of wild-type/mutant Rab4 with transferrin recycling assays; in vitro kinase assay with site-directed mutagenesis and subcellular fractionation

    PMID:1425574 PMID:1516131

    Open questions at the time
    • Effector proteins unknown
    • Whether Ser196 phosphorylation affects GTP hydrolysis not tested
  3. 1996 High

    RAB4A was placed in a compartmental map distinct from Rab7 (late endosomes) and from pericentriolar recycling endosomes, and was shown to regulate insulin-stimulated GLUT4 translocation, broadening its cargo repertoire beyond transferrin receptor.

    Evidence Immunoisolation of Rab4+ endosomes; triple-label confocal microscopy; GLUT4-myc surface assay with Rab4 mutants in adipocytes

    PMID:8790369 PMID:8910576 PMID:8943343

    Open questions at the time
    • Molecular basis of GLUT4 vesicle recognition by Rab4 unknown
    • GEF and GAP identities unknown
  4. 1997 High

    Upstream activation of RAB4A was linked to insulin signaling: PI3K-dependent GTP loading on Rab4 was demonstrated, and GDI–Rab4 complex formation was shown to be insulin-regulated, establishing the signaling input that activates Rab4 in metabolic contexts.

    Evidence GTPγS binding assay in permeabilized adipocytes with wortmannin inhibition; co-immunoprecipitation of GDI-1/GDI-2–Rab4 complexes

    PMID:9169411 PMID:9184135

    Open questions at the time
    • Identity of the PI3K-regulated GEF not determined
    • Whether GDI-1 vs GDI-2 specificity has functional consequences unknown
  5. 1998 High

    The first effector-level mechanism was revealed: Rabaptin-5 was shown to contain separate binding domains for GTP-Rab4 (N-terminal) and GTP-Rab5 (C-terminal), proposing a molecular link coordinating early endosomal sorting and internalization.

    Evidence GST pulldown, yeast two-hybrid, domain deletion analysis, immunofluorescence colocalization

    PMID:9524117

    Open questions at the time
    • Whether the dual binding occurs simultaneously on the same membrane not shown
    • No reconstituted vesicle fusion or budding assay
  6. 2000 High

    Live imaging resolved that Rab4, Rab5, and Rab11 occupy distinct but overlapping domains on continuous endosomal membranes, fundamentally redefining endosomal identity as a mosaic of Rab domains rather than discrete vesicle populations; simultaneously, RAB4A effectors Rabaptin4 and syntaxin 4 were identified.

    Evidence Multicolor live-cell GFP imaging; yeast two-hybrid and GTPase assay for Rabaptin4; co-IP and GST pulldown with nucleotide-state mutants for syntaxin 4

    PMID:10698684 PMID:10811830 PMID:11063739

    Open questions at the time
    • How Rab domains are maintained and prevented from intermixing mechanistically unknown
    • Syntaxin 4 interaction not validated in a vesicle fusion assay
  7. 2001 High

    RAB4A's cargo repertoire and effector network expanded substantially: it was shown to control rapid recycling of αvβ3 integrin (PDGF-stimulated, bypassing Rab11), formation of synaptic-like microvesicles, and sorting affecting both recycling and degradation pathways, via effectors including RCP, Rabip4, and dynein LIC-1.

    Evidence Dominant-negative Rab4 with integrin trafficking/adhesion assays; immunogold EM with budding assay in PC12 cells; yeast two-hybrid and co-IP for RCP and Rabip4; quantitative recycling/degradation assays

    PMID:11172003 PMID:11243854 PMID:11566097 PMID:11694600 PMID:11786538

    Open questions at the time
    • Motor protein engagement not reconstituted in vitro
    • How cargo selectivity is achieved among different Rab4 effectors unclear
  8. 2003 High

    A Rab4–KIF3 kinesin axis was identified for GLUT4 vesicle transport downstream of PKCλ, and CD2AP/CMS was found as a Rab4 effector linking to c-Cbl-dependent receptor degradation, revealing that Rab4 interfaces with both recycling motors and degradative sorting machinery.

    Evidence Co-IP plus microtubule capture assay with PKCλ epistasis in adipocytes; yeast two-hybrid and PDGFR degradation assay for CD2AP

    PMID:12559036 PMID:12832475

    Open questions at the time
    • Whether KIF3 directly binds Rab4-GTP or requires an adaptor not resolved
    • Structural basis of CD2AP–Rab4 interaction unknown
  9. 2004 High

    Cell-free reconstitution demonstrated that Rab4 positively regulates AP-1/clathrin-coated recycling vesicle formation from endosomes, while cholesterol accumulation (as in Niemann-Pick disease) selectively impairs GDI-mediated Rab4 extraction, linking lipid homeostasis to Rab4 cycling.

    Evidence In vitro vesicle formation assay with immunodepletion/add-back; GDI extraction assay on isolated endosomes with cholesterol manipulation

    PMID:15292453 PMID:15331762

    Open questions at the time
    • Identity of Rab4 membrane receptor still unknown
    • Whether cholesterol effect is direct or through membrane biophysical changes not distinguished
  10. 2006 High

    RAB4A was shown to directly bind CD4 and TCRζ and target them for lysosomal degradation when overexpressed, establishing a role in T-cell surface receptor homeostasis, while in cardiomyocytes it accelerated β-adrenergic receptor recycling and enhanced signaling both in vitro and in transgenic mice.

    Evidence GST pulldown, siRNA, lysosomal inhibitor studies, flow cytometry for CD4/TCRζ; receptor recycling assay, cAMP measurement, transgenic mouse model for β-AR

    PMID:16484224 PMID:16935861

    Open questions at the time
    • Whether CD4 degradation is physiological or an overexpression artifact debated
    • Mechanism distinguishing recycling vs. degradation fate for different cargoes unclear
  11. 2008 High

    Serotonylation—covalent transglutaminase-mediated serotonin attachment—was identified as a novel post-translational modification that locks Rab4 in its GTP-bound state, linking serotonin signaling to Rab4 activation and SERT intracellular retention.

    Evidence Transglutaminase-mediated serotonylation assay, co-IP, domain mapping of SERT C-terminus

    PMID:18227069

    Open questions at the time
    • Stoichiometry and site of serotonylation on Rab4 not determined
    • Whether serotonylation occurs in vivo at physiological serotonin concentrations uncertain
  12. 2009 High

    Multiple upstream regulatory inputs converged on Rab4: mTOR/NO signaling upregulated HRES-1/Rab4 in lupus T cells promoting TCRζ degradation; PKCα was shown necessary for PDGFR sorting into Rab4 domains; SGK-mediated GDI phosphorylation enhanced Rab4-dependent AMPA receptor synaptic recycling; and GRASP-1 was identified as a neuron-specific Rab4 effector essential for synaptic plasticity.

    Evidence siRNA/rapamycin in lupus T cells; PKCα epistasis with Rab4 dominant-negative; GDI phospho-mutants with electrophysiology; yeast two-hybrid plus shRNA in neurons with AMPAR recycling and spine morphology

    PMID:19201859 PMID:19369415 PMID:20051515 PMID:20098723

    Open questions at the time
    • How GRASP-1 achieves neuron specificity unknown
    • Whether mTOR-driven Rab4 upregulation is transcriptional or post-transcriptional not fully resolved
  13. 2012 High

    TBC1D16 was identified as the first bona fide GAP for Rab4A, completing the GTPase cycle by demonstrating accelerated GTP hydrolysis in vitro and showing that TBC1D16 expression reduces transferrin recycling and enhances EGFR degradation.

    Evidence In vitro GTPase assay, catalytic R494A mutant, transferrin recycling and EGFR degradation assays

    PMID:23019362

    Open questions at the time
    • Whether TBC1D16 is the sole or predominant Rab4 GAP in vivo unknown
    • Subcellular site of GAP action not precisely mapped
  14. 2014 High

    RAB4A was placed at the apex of a GTPase cascade on endosomes: Rab4→Arl1→BIG1/2→Arf1, which recruits AP-1/AP-3/GGA coat complexes, providing a mechanistic explanation for how Rab4 organizes coat-dependent sorting subdomains; additionally, Rab4 was linked to autophagosome formation and Drp1-dependent mitophagy regulation.

    Evidence Systematic siRNA epistasis analysis for the GTPase cascade; Rab4 mutant overexpression with LC3 colocalization and Drp1 Western blot in lymphocytes and lupus-prone mice

    PMID:23897774 PMID:24404161 PMID:24835460

    Open questions at the time
    • Direct physical interaction between Rab4 and Arl1 not demonstrated biochemically
    • Whether Rab4's autophagy role is independent of its recycling function unclear
  15. 2017 High

    ICMT-catalyzed carboxylmethylation was shown to be critical not only for Rab4A membrane targeting (as suggested in 1993) but specifically for effector interaction, endosomal localization, and integrin β3 recycling driving cell migration and metastasis, closing the loop between post-translational processing and functional output.

    Evidence ICMT inhibition with RAB4A localization microscopy, integrin recycling assay, in vitro migration and in vivo metastasis assays

    PMID:28604748

    Open questions at the time
    • Whether ICMT regulation is specific to Rab4 or affects many prenylated Rabs equally not fully resolved
  16. 2020 High

    Huntingtin was identified as a scaffold for Rab4-vesicle motility in axons via kinesin-1 and dynein, with polyQ-expanded HTT disrupting this transport; separately, Rab4a-dependent recycling of glucagon receptor was shown to require prior deubiquitination by USP33/STAMBP at early endosomes.

    Evidence In vivo dual-color imaging in Drosophila axons, FKBP-FRB conjugation, HD patient iNeurons; ubiquitination assays with Rab4a/Rab5a dominant-negatives and DUB siRNA

    PMID:32611447 PMID:32967969

    Open questions at the time
    • Whether HTT–Rab4 interaction is direct or via adaptor not fully resolved
    • Whether deubiquitination requirement generalizes beyond GCGR untested
  17. 2024 High

    A disease-relevant in vivo circuit was closed: constitutively active Rab4A drives CD98 recycling to the plasma membrane, activating mTOR and expanding pathogenic T-cell subsets, promoting autoantibody production and lupus nephritis; conditional Rab4A deletion in T cells or mTOR blockade rescues disease.

    Evidence Constitutively active Rab4A transgenic and conditional Rab4A knockout mice, stable isotope tracing metabolomics, flow cytometry, rapamycin treatment

    PMID:38519468

    Open questions at the time
    • Whether Rab4A-driven CD98 recycling is the sole mechanism of mTOR activation in lupus T cells not excluded
    • Human genetic validation for RAB4A variants in lupus not yet reported

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the identity of the PI3K-regulated GEF for Rab4A, the structural basis of cargo selectivity among Rab4A effectors, whether Rab4A's role in autophagy/mitophagy is mechanistically separable from its recycling function, and whether human RAB4A variants cause Mendelian or complex disease.
  • Rab4A GEF identity remains unknown
  • No high-resolution structure of Rab4A–effector complexes
  • Cargo selectivity mechanism among parallel effector pathways unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005768 endosome 5 GO:0031410 cytoplasmic vesicle 4 GO:0005829 cytosol 3
Pathway
R-HSA-5653656 Vesicle-mediated transport 6 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-9609507 Protein localization 3 R-HSA-9612973 Autophagy 2
Partners
DLCI1FMN2GRIPAP1NDRG1RAB11ARAB11FIP1RAB5ARABEP1
Complex memberships
Rab4–AP-3–rabenosyn-5–KIF3Rab4–RCP–Rab11Rab4–Rabaptin-5–Rabex-5

Evidence

Reading pass · 58 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 Rab4 protein (rab4p) is associated with the population of early endosomes involved in transferrin-receptor recycling; ~70% of rab4p co-fractionates with early endosomes and endocytic vesicles containing 125I-labeled transferrin, and the protein is tightly membrane-bound (released only by detergent). Subcellular fractionation (free-flow electrophoresis and Percoll density-gradient centrifugation), immunofluorescence, immunoblotting Proceedings of the National Academy of Sciences of the United States of America High 1906178
1992 Overexpression of wild-type Rab4 causes redistribution of transferrin receptors from endosomes to the plasma membrane and blocks iron discharge by preventing transferrin delivery to acidic early endosomes, demonstrating that Rab4 controls an early sorting/recycling event on the endocytic pathway. Stable overexpression of wild-type and mutant Rab4 in cell lines; measurement of endocytosis, transferrin recycling, and fluid-phase endocytosis Cell High 1516131
1992 Rab4 is phosphorylated at Ser196 by p34cdc2 kinase during mitosis, which causes reversible translocation of Rab4 from endosome membranes to the cytosol; mutation of Ser196 prevents phosphorylation and cytosolic accumulation without affecting isoprenylation or carboxymethylation. In vitro phosphorylation by recombinant p34cdc2, site-directed mutagenesis of Ser196, stable transfection in CHO cells, subcellular fractionation The EMBO journal High 1425574
1993 Rab4 undergoes sequential post-translational processing: isoprenylation, proteolysis, and carboxymethylation are all required for membrane association; the isoprenylated intermediate of Rab4 (unlike Rab5) requires proteolysis and carboxymethylation before it can associate with membranes. Metabolic labeling with [35S]methionine and [3H]mevalonolactone, immunoprecipitation, SDS-PAGE, Triton X-114 partitioning, subcellular fractionation Archives of biochemistry and biophysics High 8346922
1994 ERK1 (extracellular-signal-regulated kinase 1), activated by insulin, phosphorylates Rab4 at Ser196 in vitro, suggesting that insulin-induced movement of Rab4 from GLUT4-containing vesicles to the cytosol may result from ERK-mediated phosphorylation. In vitro phosphorylation using immunopurified ERK1 from insulin-stimulated 3T3-L1 adipocytes; phosphopeptide mapping European journal of biochemistry Medium 8112321
1996 Rab4 and Rab7 occupy distinct, non-overlapping endosomal compartments: immunoisolated Rab4-positive membranes contain internalized transferrin but are devoid of Rab7, placing Rab4 at early endosomes distinct from the late endosomal/lysosomal compartment. Immunoisolation of Rab4-tagged endosomes, 125I-transferrin trafficking assay, confocal immunofluorescence The Journal of biological chemistry High 8910576
1996 Rab4 and cellubrevin mark a population of early endosomes, while the pericentriolar recycling vesicle population is strikingly depleted of Rab4 (but retains cellubrevin), defining at least two biochemically distinct endosome populations on the transferrin receptor recycling pathway. Triple-label immunofluorescence confocal microscopy; brefeldin A and nocodazole pharmacological treatment Proceedings of the National Academy of Sciences of the United States of America High 8790369
1996 Rab4 participates in insulin-stimulated GLUT4 translocation in adipocytes; GTP binding (but not GTP hydrolysis) is required for Rab4 function in GLUT4 redistribution, and Rab4 associates with GLUT4-containing vesicles. Transient co-transfection of Rab4 wild-type/mutants with epitope-tagged GLUT4-myc in isolated adipocytes; cell-surface quantification of GLUT4 Molecular and cellular biology High 8943343
1996 GTPase activating protein (GAP) activity for Rab4 is enriched in plasma membrane fractions of 3T3-L1 adipocytes, suggesting that GTP hydrolysis by Rab4 occurs preferentially at the plasma membrane to regulate the Rab4 activity cycle. In vitro GTPase assay using GST-Rab4 and subcellular fractions; [α-32P]GTP hydrolysis measurement Diabetologia Medium 8858211
1997 A synthetic peptide corresponding to the Rab4 hypervariable C-terminal domain (Rab4-191–210) inhibits insulin-stimulated GLUT4 translocation and glucose transport when introduced into adipocytes, identifying the Rab4 hypervariable domain as functionally essential for GLUT4 exocytosis. Electroporation of synthetic peptides into rat adipocytes; glucose transport assay; GLUT4 immunofluorescence The Journal of biological chemistry Medium 8621647
1997 Insulin stimulates guanine nucleotide exchange (GTP loading) on Rab4 via a phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathway in rat adipocytes; wortmannin (PI3K inhibitor) abolishes insulin-stimulated GTPγS binding to Rab4 and prevents insulin-induced subcellular redistribution of Rab4. [35S]GTPγS binding assay in electrically permeabilized adipocytes; wortmannin pretreatment; subcellular fractionation The Journal of biological chemistry High 9169411
1997 Cytosolic Rab4 forms stable complexes with both GDI-1 and GDI-2 in adipocytes; insulin treatment selectively increases Rab4–GDI-1 complexes in the cytosol, providing a mechanism for insulin-regulated Rab4 membrane cycling. Co-immunoprecipitation from 3T3-L1 adipocyte lysates; immunoblotting; 32P metabolic labeling Biochemistry Medium 9184135
1997 Mitotic phosphorylation of Rab4 by cdc2/cyclin B kinase in vitro prevents Rab4 binding to its specific receptor on endosome membranes (while not affecting GDI complex formation), explaining how Rab4 accumulates in the cytosol during mitosis. In vitro reconstitution assay for Rab4 binding to purified endosomes; elastase cleavage to release soluble receptor fragment; in vitro phosphorylation by cdc2/cyclin B The EMBO journal High 9303294
1998 Rabaptin-5 contains two distinct Rab-binding domains: a C-terminal domain that binds GTP-bound Rab5, and a separate N-terminal domain that directly binds GTP-bound Rab4, proposing that Rabaptin-5 acts as a molecular linker between Rab4 and Rab5 to coordinate recycling and endocytic traffic. In vitro GST pulldown, yeast two-hybrid, domain deletion analysis, immunofluorescence colocalization The EMBO journal High 9524117
1998 Exoenzyme S from P. aeruginosa ADP-ribosylates Rab4 in reticulocyte endocytic vesicles, and this modification inhibits transferrin recycling in SLO-permeabilized reticulocytes, demonstrating that ADP-ribosylation inactivates Rab4 function. ADP-ribosylation assay with purified endocytic vesicles; transferrin recycling assay in SLO-permeabilized reticulocytes Biochemical and biophysical research communications Medium 9514923
1998 Dominant-negative Rab4 (N121I) selectively blocks receptor-mediated antigen processing in B cells without affecting fluid-phase antigen presentation, indicating that Rab4 controls a step in the early endosome-recycling pathway specifically required for processing of receptor-bound antigens. Expression of dominant-negative Rab4N121I in A20 B cells; antigen presentation assays with receptor-bound vs. fluid-phase antigens The Journal of experimental medicine High 9815254
2000 Rab4, Rab5, and Rab11 occupy distinct but overlapping domains on the same continuous endosomal membranes; three major populations exist (Rab5-only; Rab4+Rab5; Rab4+Rab11) that are dynamic but do not significantly intermix, revealing compartmentalization through Rab-domain organization. Multicolor live-cell imaging with GFP-tagged Rab proteins; transferrin as cargo; pharmacological sensitivity assays The Journal of cell biology High 10811830
2000 Rabaptin4, a novel effector of Rab4a, preferentially interacts with Rab4a-GTP (not GDP form), inhibits Rab4a's intrinsic GTPase activity, and is recruited by Rab4a-GTP to recycling endosomes enriched in cellubrevin; its N-terminal region contains the Rab4a-binding domain. Yeast two-hybrid, GST pulldown, GTPase activity assay, immunofluorescence colocalization The Biochemical journal High 10698684
2000 Rab4 regulates Ca2+-induced alpha-granule secretion (von Willebrand factor release) in platelets; Rab4 co-fractionates with alpha-granule markers, and dominant-negative Rab4(S22N) inhibits vWF secretion without affecting dense-core granule (5-HT) secretion. Density gradient centrifugation of platelet organelles; permeabilized platelet exocytosis assay with His-tagged dominant-negative Rab4S22N; rescue by Ni-bead depletion The Journal of biological chemistry High 10938270
2000 Rab4 directly interacts with syntaxin 4 in a GTP-dependent manner (GTP-bound Rab4 binds, GDP-bound does not); the interaction is inhibited by munc-18c, indicating that GTP-Rab4 binds syntaxin 4 in its open conformation and may regulate SNARE-mediated GLUT4 vesicle fusion. Co-immunoprecipitation from permeabilized adipocytes; in vitro GST-syntaxin 4 pulldown with Rab4 mutants; GTPγS/GDPβS loading; munc-18c competition assay The Journal of biological chemistry High 11063739
2001 Rab4A interacts with the central region of cytoplasmic dynein light intermediate chain-1 (LIC-1) in a nucleotide-dependent fashion; Rab4A endosomes localize to microtubules and are redistributed by nocodazole, identifying dynein as a retrograde motor linked to Rab4. Yeast two-hybrid screen, co-localization in HeLa cells, nocodazole treatment, perinuclear redistribution assay Biochemical and biophysical research communications Medium 11243854
2001 Rab coupling protein (RCP) is a novel effector that interacts specifically with GTP-bound Rab4 and also Rab11; overexpression of its C-terminal Rab-interacting domain causes dramatic transferrin compartment tubulation and significantly reduces endosomal recycling. Yeast two-hybrid, co-immunoprecipitation, immunofluorescence, quantitative transferrin recycling assay The Journal of biological chemistry High 11786538
2001 PDGF stimulates rapid Rab4-dependent recycling of αvβ3 integrin directly from early endosomes to the plasma membrane (bypassing the Rab11 recycling compartment), and inhibition by dominant-negative Rab4 mutants compromises cell adhesion and spreading on vitronectin. Dominant-negative Rab4 expression; integrin trafficking assays; cell adhesion/spreading assays on vitronectin vs. fibronectin Current biology : CB High 11566097
2001 Rab4 regulates formation of synaptic-like microvesicles from early endosomes in PC12 cells: GTPase-deficient Q67L-Rab4 increases peripheral vesicles and shifts VAMP2/TfR from endosomes, while GDP-bound S22N-Rab4 increases early endosomal tubule length. Immunogold electron microscopy, early endosome budding assays, overexpression of Rab4 mutants Molecular biology of the cell High 11694600
2001 Expression of dominant-negative Rab4(S22N) leads to significant reduction in both recycling and degradation of transferrin/EGF, and constitutively active Rab4(Q67L) induces tubulation of the transferrin compartment with varicosities positive for EEA1 and EGF, demonstrating Rab4 controls the early sorting endosomal compartment affecting both pathways. Expression of Rab4 dominant-negative and constitutively-active mutants in HeLa cells; quantitative recycling and degradation assays FEBS letters High 11322941
2001 Rabip4, a FYVE-finger-containing Rab4 effector, is present in EEA1-positive early endosomes; coexpression of Rabip4 with active Rab4 (but not inactive Rab4) causes early endosome enlargement and leads to intracellular retention of Glut1, suggesting Rabip4 controls backward transport from recycling to sorting endosomes. Yeast two-hybrid, mammalian co-localization, endosome morphology analysis, Glut1 trafficking assay Proceedings of the National Academy of Sciences of the United States of America High 11172003
2002 Rab4 function in membrane recycling requires cycling between membranes and cytosol: a chimeric Rab4 permanently attached to membranes (NHrab4cbvn) is properly targeted to early endosomes and binds guanine nucleotide normally, but fails to support efficient transcytotic transferrin receptor transport, and is still phosphorylated by a mitotic kinase. Chimeric Rab4 fused to cellubrevin transmembrane domain; transcytosis assay in MDCK cells; mitotic kinase phosphorylation assay The Journal of biological chemistry High 12036958
2002 Rab4 regulates transport to the apical plasma membrane in MDCK epithelial cells; Rab4 and GTPase-deficient Rab4Q67L redistribute transferrin receptor from basolateral to apical plasma membrane, an effect not additive with brefeldin A suggesting shared pathway. 125I-transferrin cell surface binding, subcellular fractionation, confocal immunofluorescence, brefeldin A treatment in MDCK cells The Journal of biological chemistry Medium 11790789
2003 CD2AP/CMS is a Rab4-Q67L (GTP-bound) effector that colocalizes with Rab4 and Rab7 on enlarged early endosomes; coexpression of CD2AP/CMS with Rab4-Q67L and c-Cbl is required for early endosome enlargement, and a truncated CD2AP/CMS retaining Rab4 but not c-Cbl binding inhibits PDGF receptor degradation. Yeast two-hybrid, in vitro GST pulldown, mammalian co-expression, immunofluorescence, PDGF receptor degradation assay Traffic (Copenhagen, Denmark) High 12559036
2003 Insulin-stimulated GLUT4 translocation involves PI3K-dependent PKC-λ activation, which stimulates Rab4 GTP loading; Rab4 physically associates with kinesin KIF3 (but not Rab5), and insulin increases KIF3-microtubule binding via PKC-λ, identifying a Rab4–kinesin axis for GLUT4 vesicle transport. Photoaffinity labeling ([γ-32P]GTP-azidoanilide), GST-Rab4 pulldown, co-immunoprecipitation, microtubule capture assay, dominant-negative mutant expression in 3T3-L1 adipocytes Molecular and cellular biology High 12832475
2003 Rabip4' is an 80-kDa variant of Rabip4 that binds simultaneously to GTP-bound Rab4 and GTP-bound Rab5 on early endosomes; its dominant-negative form reduces both internalization and recycling of transferrin. Biochemical characterization, co-immunoprecipitation, immunofluorescence, quantitative transferrin internalization and recycling assays Molecular biology of the cell High 14617813
2004 In vitro reconstitution shows that formation of recycling vesicles from endosomes requires AP-1/clathrin and is regulated by Rab4 (but not Rab5); depletion of rabaptin-5/rabex-5 stimulates vesicle production while addition inhibits it, placing Rab4 as a positive regulator of AP-1/clathrin-coated recycling vesicle formation. In vitro vesicle formation assay with immunodepletion of cytosolic factors, purified protein add-back, surface biotinylation Molecular biology of the cell High 15331762
2004 Elevated endosomal cholesterol in Niemann-Pick disease fibroblasts specifically inhibits Rab4-dependent (but not Rab11-dependent) membrane recycling; excess cholesterol impairs GDI-mediated extraction of Rab4 (but not Rab11) from endosomal fractions in vitro, reversed by cholesterol depletion or high-salt treatment. Dominant-negative Rab4/Rab11 expression, in vitro GDI extraction assay on isolated endosomes, cholesterol depletion, fluorescent lipid recycling assays Molecular biology of the cell High 15292453
2005 FcRn (IgG Fc receptor) leaves sorting endosomes in Rab4+Rab11+ or Rab11+ compartments; Rab4 segregates from Rab11 into discrete domains that separate, and the resulting Rab11+FcRn+ vesicle fuses with the plasma membrane — Rab4 is not involved in exocytosis. Dual-color TIRF microscopy and wide-field live imaging of GFP-tagged Rab proteins in human endothelial cells Molecular biology of the cell High 15689494
2006 HRES-1/Rab4 directly interacts with CD4 and TCRζ by pulldown; overexpression of HRES-1/Rab4 targets CD4 for lysosomal degradation and reduces surface CD4, while dominant-negative HRES-1/Rab4(S27N) enhances surface CD4 expression and recycling. GST pulldown, co-immunoprecipitation, siRNA knockdown, lysosomal inhibitor studies, flow cytometry for surface CD4 The Journal of biological chemistry High 16935861
2006 CT229, a Chlamydia trachomatis inclusion membrane protein, interacts specifically with GTP-bound Rab4A (wild-type and constitutively active Q67L, but not dominant-negative S22N) in yeast two-hybrid and colocalizes with Rab4A at the inclusion membrane, identifying CT229 as a chlamydial recruiter of Rab4A. Yeast two-hybrid screen, fluorescence colocalization in HeLa cells and C. trachomatis-infected cells Infection and immunity Medium 16926431
2006 Rab4 overexpression in cardiac myocytes markedly accelerates recycling of internalized β-adrenergic receptors to the cell surface and enhances β-AR signaling (cAMP production); transgenic overexpression of Rab4 in mouse myocardium increases plasma membrane β-AR density and augments cAMP production. Transient transfection in HL-1 cells, receptor recycling assay, cAMP measurement, transgenic mouse model The Journal of biological chemistry High 16484224
2007 NDRG1 is a Rab4a effector: it interacts specifically with constitutively active Rab4aQ67L but not GDP-bound Rab4aS22N, co-localizes with transferrin during recycling, and its knockdown delays transferrin recycling while overexpression accelerates it; NDRG1 also mediates E-cadherin recycling. In vitro reconstitution, GST pulldown with Rab4a mutants, live cell confocal microscopy, siRNA knockdown, transferrin recycling assay PloS one High 17786215
2008 Serotonin (5-HT) transamidates Rab4 and stabilizes it in the GTP-bound (active) form; Rab4-GTP then co-localizes with and binds to the serotonin transporter (SERT) at its C-terminal amino acids 616–624, retaining SERT intracellularly and reducing surface SERT density. Transglutaminase-mediated serotonylation assay, co-immunoprecipitation, co-localization imaging, C-terminal mapping by deletion analysis The Journal of biological chemistry High 18227069
2009 mTOR activation by NO in lupus T cells upregulates HRES-1/Rab4 expression; HRES-1/Rab4 overexpression promotes lysosomal degradation of TCRζ and CD4, and siRNA knockdown of HRES-1/Rab4 or lysosomal inhibition restores TCRζ levels. siRNA knockdown, flow cytometry, Western blot, rapamycin treatment in vivo; pull-down studies showing direct interaction with CD4 and TCRζ Journal of immunology High 19201859
2009 B2AR signaling via PKA and a specific PKA phosphorylation site on the B2AR C-tail regulates the frequency of Rab4-dependent rapid recycling events; agonist removal increases recycling event frequency ~2-fold within 1 minute, and this is dependent on cAMP/PKA-mediated receptor signaling. TIRF microscopy with pH-sensitive GFP-tagged B2AR; pharmacological PKA inhibition; B2AR C-tail phosphorylation site mutants Molecular biology of the cell High 19369423
2009 PKCα activation is required for sorting of the PDGF β-receptor into Rab4a-positive domains on early endosomes for recycling; PKCα inhibition prevents receptor entry into Rab4a domains, and dominant-negative Rab4aS22N blocks recycling, identifying a PKCα→Rab4a sequential pathway. Dominant-negative Rab4a mutant expression, PKCα knockdown/inhibition, receptor trafficking assays, fluorescence microscopy Molecular biology of the cell High 19369415
2009 D-AKAP2/AKAP10 RGS domains interact with GTP-bound Rab4 and Rab11; D-AKAP2 knockdown increases the rate of transferrin recycling and redistributes Rab11 and transferrin receptor to the cell periphery, implicating D-AKAP2 as a regulator that retains recycling cargoes in Rab4/Rab11-positive compartments. Yeast two-hybrid, GST pulldown with Rab4/Rab11 mutants, siRNA knockdown, transferrin recycling assay, immunofluorescence The Journal of biological chemistry High 19797056
2009 Corticosterone, via SGK phosphorylation of GDI at Ser-213, increases GDI–Rab4 complex formation, facilitating Rab4 functional cycling and Rab4-dependent recycling of AMPA receptors to the synaptic membrane in prefrontal cortex neurons. Co-immunoprecipitation, GDI Ser213 phospho-mutants, AMPAR synaptic current recording, surface expression assays The Journal of biological chemistry High 20051515
2009 VEGFR1 engagement activates a Rab4A-dependent pathway that transports αvβ3 integrin from early endosomes to the plasma membrane, required for VEGF-driven fibronectin polymerization and endothelial tube branching in angiogenesis. Dominant-negative Rab4A expression, integrin recycling assay, fibronectin polymerization assay, organotypic tubule branching assay Traffic (Copenhagen, Denmark) High 19302266
2010 GRASP-1 is a neuron-specific Rab4 effector that segregates Rab4 from EEA1/Neep21/Rab5-positive early endosomal membranes, couples to Rab11 recycling endosomes via interaction with syntaxin 13, and is necessary for AMPA receptor recycling, spine morphology maintenance, and synaptic plasticity. Yeast two-hybrid, co-immunoprecipitation, shRNA knockdown in neurons, AMPAR recycling assay, electrophysiology, dendritic spine morphology analysis PLoS biology High 20098723
2012 TBC1D16 is a GTPase activating protein (GAP) for Rab4A that enhances Rab4A intrinsic GTP hydrolysis rate in vitro; TBC1D16 expression reduces transferrin receptor recycling (without affecting internalization), alters GFP-Rab4A membrane localization, and enhances EGF-stimulated EGFR degradation. In vitro GTPase activity assay, dominant-negative R494A GAP mutant, transferrin recycling assay, EGFR degradation assay Proceedings of the National Academy of Sciences of the United States of America High 23019362
2013 HRES-1/Rab4 overexpression depletes Drp1 protein levels and increases mitochondrial mass in lymphocytes; dominant-negative HRES-1/Rab4(S27N) abrogates these effects; geranylgeranyl transferase inhibition restores Drp1 and reduces mitochondrial accumulation in lupus-prone mice. Western blot, flow cytometry, microscopy, overexpression/dominant-negative constructs in Jurkat cells and PBL, MRL/lpr mouse model Annals of the rheumatic diseases High 23897774
2014 HRES-1/Rab4 promotes formation of LC3+ autophagosomes and accumulation of mitochondria during autophagy; constitutively active Q72L promotes mitochondrial tubular network formation; dominant-negative S27N reduces LC3 colocalization; a C-terminally truncated native isoform Rab4(1-121) enhances autophagosome formation without starvation. Overexpression of Rab4 isoforms/mutants, fluorescence colocalization, autophagy induction by starvation/rapamycin PloS one Medium 24404161
2014 Rab4 orchestrates a GTPase cascade on early endosomes: Rab4 recruits Arl1; Arl1 promotes recruitment of BIG1/BIG2 (Arf-GEFs); BIG1/BIG2 activate Arf1/Arf3; Arf1 is required for AP-1, AP-3, and GGA-3 recruitment; Arl1 depletion randomizes Rab4 distribution and inhibits tubular subdomain formation. siRNA knockdown of pathway components, brefeldin A inhibition, immunofluorescence microscopy, epistasis analysis Current biology : CB High 24835460
2014 RAB5A promotes RAB4-dependent endo/exocytic cycles (EECs) of MT1-MMP and β3 integrin required for invadosome formation; RAB5A is necessary for RAB4- and RABENOSYN-5-dependent cycling of these cargoes driving proteolytic invasive chemotaxis in vitro and conversion of DCIS to IDC in vivo. siRNA knockdown, dominant-negative Rab mutants, cargo trafficking assays, invadosome formation assay, xenograft in vivo model The Journal of cell biology High 25049275
2015 Rabaptin5 membrane recruitment requires binding to both Rab4 and Rabex5, not Rab5; deletion of either Rab5-binding domain or Rab5 silencing does not affect Rabaptin5 recruitment but produces giant endosomes, contradicting the Rab5 positive-feedback model and indicating Rab4 drives Rabaptin5 recruitment to activate Rab5 in a feed-forward manner. Deletion analysis by co-immunoprecipitation, Rab5 siRNA silencing, endosome morphology analysis Journal of cell science High 26430212
2017 ICMT-catalyzed carboxylmethylation of RAB4A is critical for RAB4A activation, interaction with effectors, localization to endosomes and recycling vesicles, and RAB4A-dependent integrin β3 recycling to the plasma membrane; ICMT inhibition reduces cell migration and cancer metastasis. ICMT inhibition, RAB4A localization by fluorescence microscopy, integrin β3 recycling assay, in vitro migration and in vivo metastasis assays Oncogene High 28604748
2017 Serotonylation of Rab4 (covalent 5-HT modification) activates the GTPase and improves glucose metabolism in skeletal muscle cells; inhibition of protein serotonylation blocks 5-HT-induced GLUT4 translocation and glucose uptake. Serotonylation assay identifying ~25 kDa Rab4 band, deoxyglucose uptake assay, GLUT4 translocation assay, monodansylcadaverine inhibition Diabetology & metabolic syndrome Medium 28053672
2018 Rab4A localizes to sorting endosomes and forms a complex with AP-3, rabenosyn-5, and KIF3 to coordinate cargo segregation; Rab4A depletion in melanocytes causes defective melanosome maturation, misdirection of melanosomal proteins to lysosomes/exosomes/cell surface, and increased vacuolar endosomes. RNAi screening, co-immunoprecipitation, immunofluorescence, cargo sorting assays in melanocytes Journal of cell science High 30154210
2020 HTT (huntingtin) physically associates with Rab4-containing vesicles in axons and is required for bi-directional Rab4 motility via kinesin-1, dynein, and the accessory protein HIP1; polyQ-expanded HTT disrupts HTT-Rab4 vesicle motility causing synaptic accumulations, aberrant morphology, and locomotion defects rescued by excess Rab4. In vivo dual-color imaging in Drosophila axons, FKBP-FRB conjugation assay in rat fibroblasts, genetic rescue, iNeuron analysis from HD patients Acta neuropathologica communications High 32611447
2020 Agonist-activated glucagon receptors (GCGR) are deubiquitinated at early endosomes by USP33 and STAMBP, and this deubiquitination is required for Rab4a-dependent recycling; a Rab4a dominant-negative that blocks recycling endosomes enables deubiquitination, while a Rab5a DN that blocks early endosomes eliminates it. Endocytic colocalization assays, ubiquitination assays, Rab4a/Rab5a dominant-negative expression, siRNA knockdown of deubiquitinases, GCGR lysine-to-arginine mutant The Journal of biological chemistry High 32967969
2024 Constitutively active Rab4AQ72L drives CD98 receptor recycling to the plasma membrane, increasing kynurenine-producing CD98 expression and mTOR activation; this expands CD4+ and DN T cells, promotes B cell activation and autoantibody production; Rab4A deletion or mTOR blockade restrains CD98 expression and attenuates glomerulonephritis in lupus-prone mice. Constitutively active Rab4A transgenic mice, conditional Rab4A knockout in T cells, stable isotope tracing metabolomics, flow cytometry, CD98 surface trafficking assay, rapamycin treatment Nature communications High 38519468

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Distinct membrane domains on endosomes in the recycling pathway visualized by multicolor imaging of Rab4, Rab5, and Rab11. The Journal of cell biology 836 10811830
1992 The small GTP-binding protein rab4 controls an early sorting event on the endocytic pathway. Cell 581 1516131
2001 PDGF-regulated rab4-dependent recycling of alphavbeta3 integrin from early endosomes is necessary for cell adhesion and spreading. Current biology : CB 313 11566097
1996 Rab4 and cellubrevin define different early endosome populations on the pathway of transferrin receptor recycling. Proceedings of the National Academy of Sciences of the United States of America 289 8790369
1991 The small GTP-binding protein rab4 is associated with early endosomes. Proceedings of the National Academy of Sciences of the United States of America 273 1906178
2009 Activation of mammalian target of rapamycin controls the loss of TCRzeta in lupus T cells through HRES-1/Rab4-regulated lysosomal degradation. Journal of immunology (Baltimore, Md. : 1950) 214 19201859
1998 Distinct Rab-binding domains mediate the interaction of Rabaptin-5 with GTP-bound Rab4 and Rab5. The EMBO journal 195 9524117
2013 HRES-1/Rab4-mediated depletion of Drp1 impairs mitochondrial homeostasis and represents a target for treatment in SLE. Annals of the rheumatic diseases 155 23897774
2005 From sorting endosomes to exocytosis: association of Rab4 and Rab11 GTPases with the Fc receptor, FcRn, during recycling. Molecular biology of the cell 147 15689494
2001 Rab4 affects both recycling and degradative endosomal trafficking. FEBS letters 146 11322941
2002 Rab coupling protein (RCP), a novel Rab4 and Rab11 effector protein. The Journal of biological chemistry 141 11786538
2003 Insulin-induced GLUT4 translocation involves protein kinase C-lambda-mediated functional coupling between Rab4 and the motor protein kinesin. Molecular and cellular biology 139 12832475
1992 Reversible phosphorylation--dephosphorylation determines the localization of rab4 during the cell cycle. The EMBO journal 128 1425574
2006 The GTPase Rab4 interacts with Chlamydia trachomatis inclusion membrane protein CT229. Infection and immunity 122 16926431
2003 CD2AP/CMS regulates endosome morphology and traffic to the degradative pathway through its interaction with Rab4 and c-Cbl. Traffic (Copenhagen, Denmark) 115 12559036
2014 A RAB5/RAB4 recycling circuitry induces a proteolytic invasive program and promotes tumor dissemination. The Journal of cell biology 114 25049275
2004 Elevated endosomal cholesterol levels in Niemann-Pick cells inhibit rab4 and perturb membrane recycling. Molecular biology of the cell 114 15292453
2007 The N-Myc down regulated Gene1 (NDRG1) Is a Rab4a effector involved in vesicular recycling of E-cadherin. PloS one 106 17786215
1996 Potential role of Rab4 in the regulation of subcellular localization of Glut4 in adipocytes. Molecular and cellular biology 101 8943343
2000 Small GTPase Rab4 regulates Ca2+-induced alpha-granule secretion in platelets. The Journal of biological chemistry 91 10938270
2009 Intracellular trafficking of the human oxytocin receptor: evidence of receptor recycling via a Rab4/Rab5 "short cycle". American journal of physiology. Endocrinology and metabolism 90 19126785
2010 Neuron specific Rab4 effector GRASP-1 coordinates membrane specialization and maturation of recycling endosomes. PLoS biology 89 20098723
2009 Cargo-mediated regulation of a rapid Rab4-dependent recycling pathway. Molecular biology of the cell 88 19369423
2001 A FYVE-finger-containing protein, Rabip4, is a Rab4 effector involved in early endosomal traffic. Proceedings of the National Academy of Sciences of the United States of America 86 11172003
2001 The small GTPase Rab4A interacts with the central region of cytoplasmic dynein light intermediate chain-1. Biochemical and biophysical research communications 81 11243854
1998 Complexity of trypanosomatid endocytosis pathways revealed by Rab4 and Rab5 isoforms in Trypanosoma brucei. The Journal of biological chemistry 79 9822686
1996 Rab4 and Rab7 define distinct nonoverlapping endosomal compartments. The Journal of biological chemistry 74 8910576
2004 In vitro formation of recycling vesicles from endosomes requires adaptor protein-1/clathrin and is regulated by rab4 and the connector rabaptin-5. Molecular biology of the cell 72 15331762
1997 The small guanosine triphosphate-binding protein Rab4 is involved in insulin-induced GLUT4 translocation and actin filament rearrangement in 3T3-L1 cells. Endocrinology 67 9348225
2024 Rab4A-directed endosome traffic shapes pro-inflammatory mitochondrial metabolism in T cells via mitophagy, CD98 expression, and kynurenine-sensitive mTOR activation. Nature communications 64 38519468
2014 Rab4 orchestrates a small GTPase cascade for recruitment of adaptor proteins to early endosomes. Current biology : CB 63 24835460
2006 Regulation of CD4 expression via recycling by HRES-1/RAB4 controls susceptibility to HIV infection. The Journal of biological chemistry 63 16935861
2001 Rab4 regulates formation of synaptic-like microvesicles from early endosomes in PC12 cells. Molecular biology of the cell 61 11694600
1996 A synthetic peptide corresponding to the Rab4 hypervariable carboxyl-terminal domain inhibits insulin action on glucose transport in rat adipocytes. The Journal of biological chemistry 59 8621647
2011 Metformin induces Rab4 through AMPK and modulates GLUT4 translocation in skeletal muscle cells. Journal of cellular physiology 58 20857458
2004 Regulation of cardiac contractility by Rab4-modulated beta2-adrenergic receptor recycling. Proceedings of the National Academy of Sciences of the United States of America 58 15105445
2003 Rabip4' is an effector of rab5 and rab4 and regulates transport through early endosomes. Molecular biology of the cell 58 14617813
2010 The stress hormone corticosterone increases synaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors via serum- and glucocorticoid-inducible kinase (SGK) regulation of the GDI-Rab4 complex. The Journal of biological chemistry 57 20051515
1996 A role for a Rab4-like GTPase in endocytosis and in regulation of contractile vacuole structure and function in Dictyostelium discoideum. Molecular biology of the cell 55 8898366
2009 D-AKAP2 interacts with Rab4 and Rab11 through its RGS domains and regulates transferrin receptor recycling. The Journal of biological chemistry 53 19797056
2000 Rabaptin4, a novel effector of the small GTPase rab4a, is recruited to perinuclear recycling vesicles. The Biochemical journal 53 10698684
1996 Differential effects of insulin and exercise on Rab4 distribution in rat skeletal muscle. Endocrinology 53 8536622
1994 A Rab4-like GTPase in Dictyostelium discoideum colocalizes with V-H(+)-ATPases in reticular membranes of the contractile vacuole complex and in lysosomes. Journal of cell science 53 7876348
1997 Insulin stimulates guanine nucleotide exchange on Rab4 via a wortmannin-sensitive signaling pathway in rat adipocytes. The Journal of biological chemistry 50 9169411
2017 Serotonin improves glucose metabolism by Serotonylation of the small GTPase Rab4 in L6 skeletal muscle cells. Diabetology & metabolic syndrome 46 28053672
2008 Serotonin transamidates Rab4 and facilitates its binding to the C terminus of serotonin transporter. The Journal of biological chemistry 46 18227069
2006 Enhancement of the recycling and activation of beta-adrenergic receptor by Rab4 GTPase in cardiac myocytes. The Journal of biological chemistry 46 16484224
2014 HRES-1/Rab4 promotes the formation of LC3(+) autophagosomes and the accumulation of mitochondria during autophagy. PloS one 44 24404161
2002 Rab4 function in membrane recycling from early endosomes depends on a membrane to cytoplasm cycle. The Journal of biological chemistry 43 12036958
1997 Mitotic phosphorylation of rab4 prevents binding to a specific receptor on endosome membranes. The EMBO journal 42 9303294
2012 Spinal SGK1/GRASP-1/Rab4 is involved in complete Freund's adjuvant-induced inflammatory pain via regulating dorsal horn GluR1-containing AMPA receptor trafficking in rats. Pain 41 22980744
2009 Activation of protein kinase C alpha is necessary for sorting the PDGF beta-receptor to Rab4a-dependent recycling. Molecular biology of the cell 40 19369415
2009 VEGFR1 (Flt1) regulates Rab4 recycling to control fibronectin polymerization and endothelial vessel branching. Traffic (Copenhagen, Denmark) 39 19302266
2000 Direct interaction of Rab4 with syntaxin 4. The Journal of biological chemistry 39 11063739
1995 Rab4, but not the transferrin receptor, is colocalized with GLUT4 in an insulin-sensitive intracellular compartment in rat skeletal muscle. Biochemical and biophysical research communications 39 7575609
2010 Rab GTPases bind at a common site within the angiotensin II type I receptor carboxyl-terminal tail: evidence that Rab4 regulates receptor phosphorylation, desensitization, and resensitization. Molecular pharmacology 38 20943774
1998 The monomeric guanosine triphosphatase rab4 controls an essential step on the pathway of receptor-mediated antigen processing in B cells. The Journal of experimental medicine 37 9815254
2010 Deregulation of Rab5 and Rab4 proteins in p85R274A-expressing cells alters PDGFR trafficking. Cellular signalling 36 20570729
2008 Rab4 and Rab11 coordinately regulate the recycling of angiotensin II type I receptor as demonstrated by fluorescence resonance energy transfer microscopy. Journal of biomedical optics 36 18601530
2012 TBC1D16 is a Rab4A GTPase activating protein that regulates receptor recycling and EGF receptor signaling. Proceedings of the National Academy of Sciences of the United States of America 35 23019362
2002 rab4 regulates transport to the apical plasma membrane in Madin-Darby canine kidney cells. The Journal of biological chemistry 35 11790789
2006 The Rab4 effector Rabip4 plays a role in the endocytotic trafficking of Glut 4 in 3T3-L1 adipocytes. Journal of cell science 34 16522682
2004 Rab4 is an essential regulator of lysosomal trafficking in trypanosomes. The Journal of biological chemistry 34 15284229
1994 Rab4 is phosphorylated by the insulin-activated extracellular-signal-regulated kinase ERK1. European journal of biochemistry 34 8112321
1993 Post-translational processing and membrane association of the two early endosome-associated rab GTP-binding proteins (rab4 and rab5). Archives of biochemistry and biophysics 34 8346922
2018 Rab4A organizes endosomal domains for sorting cargo to lysosome-related organelles. Journal of cell science 32 30154210
2005 Rab4 GTP/GDP modulates amiloride-sensitive sodium channel (ENaC) function in colonic epithelia. Biochemical and biophysical research communications 32 16389071
1999 Involvement of Rab4 in regulated exocytosis of rat pancreatic acini. Gastroenterology 32 10092317
2017 Anterograde Transport of Rab4-Associated Vesicles Regulates Synapse Organization in Drosophila. Cell reports 31 28273459
2015 Rabaptin5 is recruited to endosomes by Rab4 and Rabex5 to regulate endosome maturation. Journal of cell science 31 26430212
2015 Laminar Shear Stress Promotes Vascular Endothelial Cell Autophagy Through Upregulation with Rab4. DNA and cell biology 31 26716952
2020 Excess Rab4 rescues synaptic and behavioral dysfunction caused by defective HTT-Rab4 axonal transport in Huntington's disease. Acta neuropathologica communications 30 32611447
2000 Expression of a prenylation-deficient Rab4 interferes with propagation of insulin signaling through insulin receptor substrate-1. Endocrinology 30 10614641
2013 Regulation of the human ether-a-go-go-related gene (hERG) channel by Rab4 protein through neural precursor cell-expressed developmentally down-regulated protein 4-2 (Nedd4-2). The Journal of biological chemistry 29 23792956
2011 Rab4 interacts with the human P-glycoprotein and modulates its surface expression in multidrug resistant K562 cells. International journal of cancer 29 20209493
2004 Endosomal ricin transport: involvement of Rab4- and Rab5-positive compartments. Histochemistry and cell biology 28 15221413
2012 The Bro1-domain-containing protein Myopic/HDPTP coordinates with Rab4 to regulate cell adhesion and migration. Journal of cell science 27 22825871
2006 The Rab4A effector protein Rabip4 is involved in migration of NIH 3T3 fibroblasts. The Journal of biological chemistry 27 17001082
2011 Procathepsin L secretion, which triggers tumour progression, is regulated by Rab4a in human melanoma cells. The Biochemical journal 26 21501115
2010 Akt2 deficiency promotes cardiac induction of Rab4a and myocardial β-adrenergic hypersensitivity. Journal of molecular and cellular cardiology 26 20728450
2017 Isoprenylcysteine carboxylmethyltransferase function is essential for RAB4A-mediated integrin β3 recycling, cell migration and cancer metastasis. Oncogene 25 28604748
2008 Phosphorylation state of mu-opioid receptor determines the alternative recycling of receptor via Rab4 or Rab11 pathway. Molecular endocrinology (Baltimore, Md.) 25 18550774
2000 Regulation of subcellular distribution of GLUT4 in cardiomyocytes: Rab4A reduces basal glucose transport and augments insulin responsiveness. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association 24 10768829
2001 Expression of a prenylation-deficient Rab4 inhibits the GLUT4 translocation induced by active phosphatidylinositol 3-kinase and protein kinase B. The Biochemical journal 23 11336646
1997 Association of cytosolic Rab4 with GDI isoforms in insulin-sensitive 3T3-L1 adipocytes. Biochemistry 23 9184135
1997 Heterologous expression of rab4 reduces glucose transport and GLUT4 abundance at the cell surface in oocytes. The Biochemical journal 22 9182703
2020 Complex Rab4-Mediated Regulation of Endosomal Size and EGFR Activation. Molecular cancer research : MCR 21 32019812
2020 Agonist-activated glucagon receptors are deubiquitinated at early endosomes by two distinct deubiquitinases to facilitate Rab4a-dependent recycling. The Journal of biological chemistry 18 32967969
2014 Rab11, but not Rab4, facilitates cyclic AMP- and tauroursodeoxycholate-induced MRP2 translocation to the plasma membrane. American journal of physiology. Gastrointestinal and liver physiology 18 25190474
2007 Rab4A GTPase catenin interactions are involved in cell junction dynamics in the testis. Journal of andrology 18 17494101
1998 Exoenzyme S from P. aeruginosa ADP ribosylates rab4 and inhibits transferrin recycling in SLO-permeabilized reticulocytes. Biochemical and biophysical research communications 18 9514923
2020 Lupus-associated endogenous retroviral LTR polymorphism and epigenetic imprinting promote HRES-1/RAB4 expression and mTOR activation. JCI insight 17 31805010
2019 Cytoskeleton Protein Filamin A Is Required for Efficient Somatostatin Receptor Type 2 Internalization and Recycling through Rab5 and Rab4 Sorting Endosomes in Tumor Somatotroph Cells. Neuroendocrinology 16 31574507
2003 Co-localization of rab4 with endocytosis-related proteins in the rat parotid glands. Archives of histology and cytology 16 12703553
2023 Proximity labelling identifies pro-migratory endocytic recycling cargo and machinery of the Rab4 and Rab11 families. Journal of cell science 15 37232246
1996 GTPase activating protein activity for Rab4 is enriched in the plasma membrane of 3T3-L1 adipocytes. Possible involvement in the regulation of Rab4 subcellular localization. Diabetologia 15 8858211
2008 Rab4 facilitates cyclic adenosine monophosphate-stimulated bile acid uptake and Na+-taurocholate cotransporting polypeptide translocation. Hepatology (Baltimore, Md.) 14 18688880
2015 RhoGAP68F controls transport of adhesion proteins in Rab4 endosomes to modulate epithelial morphogenesis of Drosophila leg discs. Developmental biology 13 25617722
2005 The Rab5 effector Rabaptin-5 and its isoform Rabaptin-5delta differ in their ability to interact with the small GTPase Rab4. The FEBS journal 13 15634330
1997 Rab4 associates with the actin terminal web in developing rat pancreatic acinar cells. European journal of cell biology 12 9013719