| 2002 |
Rab13 is recruited to junctional complexes from a cytosolic pool after cell-cell contact formation. Constitutively active Rab13 (Q67L) delays formation of electrically tight epithelial monolayers, disrupts the tight junction fence diffusion barrier, and delays claudin-1 localization at the cell surface, while inactive Rab13 (T22N) has no effect on TJ function or structure. |
Stable GFP-Rab13 mutant cell lines (Q67L and T22N) in MDCK cells; transepithelial electrical resistance; freeze-fracture EM; immunofluorescence; tracer leakage assays |
Molecular biology of the cell |
High |
12058051
|
| 1998 |
The rod cGMP phosphodiesterase delta subunit (delta-PDE) specifically binds Rab13 and purified recombinant delta-PDE dissociates Rab13 from cellular membranes, suggesting delta-PDE (not GDI) controls the dynamic association of Rab13 with membranes. |
Yeast two-hybrid screen of HeLa cDNA library; purified recombinant delta-PDE membrane dissociation assay; immunofluorescence |
The Journal of biological chemistry |
Medium |
9712853
|
| 2004 |
Rab13 dominant active mutant (Q67L) specifically inhibits postendocytic recycling of occludin back to the cell surface, but not recycling of transferrin receptor or polymeric immunoglobulin receptor; endocytosed occludin colocalizes with Rab13. |
Cell surface biotinylation; biochemical endocytosis and recycling assays; double immunolabeling; dominant active Rab13 expression in BHK and MTD-1A cells |
The Journal of biological chemistry |
High |
15528189
|
| 2004 |
GTP-bound Rab13 directly binds to the alpha-catalytic subunit of PKA and inhibits PKA activity, thereby preventing PKA-dependent phosphorylation and tight junction recruitment of VASP (vasodilator-stimulated phosphoprotein). Activation of PKA abrogates the inhibitory effect of Rab13 on recruitment of VASP, ZO-1, and claudin-1 to cell-cell junctions. |
Co-immunoprecipitation; in vitro PKA activity assay with purified Rab13; dominant active Rab13 expression; PKA activator rescue experiments |
The Journal of cell biology |
High |
15096524 16473634
|
| 2006 |
MICAL-L2 (renamed JRAB, junctional Rab13-binding protein) specifically binds to the GTP-bound form of Rab13 via its C-terminal coiled-coil domain, localizes to tight junctions, and mediates endocytic recycling of occludin and formation of functional tight junctions. A MICAL-L2 mutant lacking the Rab13-binding domain (MICAL-L2-N) inhibits occludin recycling and TJ formation. MICAL-L2 links Rab13 to the actin cytoskeleton and is displaced from TJs upon actin depolymerization. |
Yeast two-hybrid; immunoprecipitation; immunofluorescence; recycling assay; Ca2+ switch assay; transepithelial electrical resistance measurement |
Molecular biology of the cell |
High |
16525024
|
| 2007 |
JRAB/MICAL-L2 interacts with both Rab13 and Rab8 via its C-terminal domain, with Rab8 and Rab13 competing for MICAL-L2 binding. Rab13 specifically mediates claudin-1 and occludin transport to the plasma membrane but not E-cadherin transport, while Rab8 mediates Rab13-independent E-cadherin transport. JRAB/MICAL-L2 coordinates TJ and AJ assembly by sequentially interacting with Rab8 at perinuclear recycling compartments and Rab13 at the plasma membrane. |
siRNA knockdown; Ca2+ switch model; co-immunoprecipitation; immunofluorescence; dominant-negative and constitutively active mutant expression |
Molecular biology of the cell |
High |
18094055
|
| 2008 |
Rab13 regulates membrane trafficking between the trans-Golgi network (TGN) and recycling endosomes (RE). Rab13 partially colocalizes with TGN38 at the TGN and transferrin receptors in RE. Knockdown or dominant mutant expression of Rab13 disrupts TGN38/46 localization and inhibits surface arrival of proteins that transit through RE (VSVG, A-VSVG, LDLR-CT27), but not proteins using a direct TGN-to-PM route. |
shRNA knockdown in HBE cells; dominant-active and dominant-negative allele overexpression in MDCK cells; immunofluorescence colocalization; surface protein arrival assays |
The Journal of cell biology |
High |
18779367
|
| 2009 |
Rab13 regulates neurite outgrowth in PC12 cells through its effector JRAB/MICAL-L2. Rab13 binding to JRAB/MICAL-L2 stimulates an intramolecular conformational change in JRAB/MICAL-L2 and promotes its interaction with actinin-4, an actin-binding protein that localizes to the cell body and neurite tips. This complex is proposed to transfer actinin-4 to neurite tips to reorganize actin for neurite extension. |
Dominant active Rab13 expression; co-immunoprecipitation; immunofluorescence; neurite outgrowth assays in PC12 cells |
Molecular and cellular biology |
Medium |
20008558
|
| 2010 |
Insulin promotes GTP loading of Rab13 (and Rab8A) in rat L6 muscle cells. siRNA-mediated Rab13 knockdown blocks insulin-induced GLUT4 appearance at the muscle cell surface, rescued by Rab13 ortholog but not Rab8A. Constitutively active AS160 (Rab-GAP) suppresses surface GLUT4, reversed by Rab13 or Rab8A overexpression, placing both Rabs downstream of AS160 in GLUT4 exocytic trafficking. Insulin promotes Rab13 colocalization with GLUT4 at the cell periphery. |
GTP-loading assay; siRNA knockdown; surface GLUT4 measurement; constitutively active AS160 expression; immunofluorescence colocalization |
Proceedings of the National Academy of Sciences of the United States of America |
High |
21041651
|
| 2011 |
Rab13 is required for trafficking of a protein complex (RhoA, Syx, Mupp1, angiomotin) to the leading edge of migrating endothelial cells. Rab13 associates with Grb2, targeting Syx and RhoA to Tyr1175-phosphorylated VEGFR2 at the leading edge. Rab13 knockdown in zebrafish impedes sprouting of intersegmental vessels and reduces tip cell directionality. |
siRNA knockdown; co-immunoprecipitation; live-cell imaging; zebrafish vessel sprouting assay; directed migration assay |
The Journal of biological chemistry |
Medium |
21543326
|
| 2012 |
JRAB/MICAL-L2 interacts with actin-binding proteins actinin-1 and actinin-4 and filamentous actin via different domains, regulating actin cross-linking and stabilization. During epithelial junctional development, JRAB is enriched in the actin bundle at the free border; Rab13 binding induces a conformational change in JRAB required for maturation of cell-cell adhesion sites. |
Co-immunoprecipitation; immunofluorescence; actin bundling assays; dominant active Rab13 expression; Ca2+ switch assay |
The Journal of biological chemistry |
Medium |
23100251
|
| 2014 |
Rab35 functions as a master Rab that recruits MICAL-L1 to Arf6-positive recycling endosomes, and MICAL-L1 in turn recruits Rab13 (along with Rab8 and Rab36) to these endosomes during NGF-induced neurite outgrowth in PC12 cells. Rab13 regulates neurite outgrowth non-redundantly downstream of Rab35 and MICAL-L1. |
Dominant active/negative Rab mutant expression; siRNA knockdown; immunofluorescence; neurite outgrowth assays in PC12 cells |
Biology open |
Medium |
25086062
|
| 2014 |
In lymphocytes, chemokine stimulation activates Rab13 via DENND1C (a GEF phosphorylated by kinase Mst1). Active Rab13 associates with Mst1 to facilitate delivery of integrin LFA-1 to the leading edge, involving myosin Va recruitment along actin filaments. Rab13-deficient mice have reduced lymphocyte numbers in lymphoid tissues due to defective trafficking. Inhibiting Rab13 function reduces lymphocyte adhesion and migration on ICAM-1 and disrupts the ring-like LFA-1 arrangement at the T cell-APC contact site. |
DENND1C phosphorylation assays; Rab13 activation assays; Rab13 knockout mice; LFA-1 surface trafficking assays; lymphocyte adhesion and migration assays; immunofluorescence |
Science signaling |
High |
25074980
|
| 2015 |
DENND2B is the guanine nucleotide exchange factor (GEF) for Rab13. DENND2B activates Rab13 specifically at the leading edge of migrating cells, as demonstrated by a FRET-based Rab13 biosensor. DENND2B interacts with the Rab13 effector MICAL-L2 at the cell periphery, and this interaction is required for dynamic remodeling of the leading edge. Disruption of Rab13-mediated trafficking limits invasive behavior in vitro and growth/migration of cancer cells in vivo. |
FRET-based Rab13 biosensor; GEF activity assay; co-immunoprecipitation; in vitro invasion assays; in vivo tumor xenograft assays |
The Journal of cell biology |
High |
25713415
|
| 2015 |
Rab13 forms an insulin-dependent complex with MICAL-L2 and alpha-actinin-4 (ACTN4) in muscle cells. Insulin increases Rab13 binding to MICAL-L2, which in turn binds ACTN4. GLUT4 associates with this complex in response to insulin, requiring the ACTN4-binding domain in MICAL-L2. Knockdown of MICAL-L2 or expression of truncated MICAL-L2 impairs insulin-stimulated GLUT4 translocation. |
Pull-down assays; confocal fluorescence microscopy; structured illumination microscopy (SIM); TIRF microscopy; siRNA knockdown; co-immunoprecipitation |
Molecular biology of the cell |
High |
26538022
|
| 2016 |
C-terminal prenylation is not required for Rab13 to associate with and traffic on vesicles in its inactive GDP-bound state; inactive Rab13 associates with vesicles via protein-protein interactions. Only upon activation does Rab13 associate with the plasma membrane, presumably via C-terminal prenyl group membrane insertion. |
Prenylation-deficient Rab13 mutant expression; subcellular fractionation; live-cell vesicle trafficking imaging |
The Journal of biological chemistry |
Medium |
26969162
|
| 2017 |
Rab13 is required for ionomycin-stimulated GLUT4 exocytosis in L6 myoblasts. siRab13 (but not siRab8a, siRab10, or siRab14) selectively inhibited GLUT4 exocytosis promoted by elevated cytosolic Ca2+, placing Rab13 specifically downstream of Ca2+/PKC signaling in this pathway. |
siRNA knockdown; surface GLUT4myc exocytosis assay; ionomycin-stimulated Ca2+ elevation; phosphorylation assays for AS160 and TBC1D1 |
Biochemical and biophysical research communications |
Medium |
29247648
|
| 2017 |
Electrical pulse stimulation (EPS)-induced GLUT4 translocation in C2C12 myotubes requires Rab8a, Rab13, and Rab14 but not Rab10. Rab10 and Rab13 are not engaged by AMPK activation alone. Constitutively active AS160 diminishes EPS-stimulated GLUT4 translocation, supporting regulation downstream of Rab-GAP AS160. |
siRNA knockdown; surface HA-GLUT4 measurement; EPS contraction model; constitutively active AS160 expression; AMPK inhibitor and siRNA treatments |
American journal of physiology. Endocrinology and metabolism |
Medium |
29089333
|
| 2019 |
RAB13 and GGA2 (Golgi-localized gamma ear-containing Arf-binding protein 2) both regulate activity-dependent recycling of active but not inactive beta1-integrin to the plasma membrane. RAB13 silencing triggers intracellular accumulation of active beta1-integrin and reduces integrin activity in focal adhesions and cell migration. GGA2 and RAB13 interact (identified by BioID proximity labeling). |
RNAi screen; BioID proximity labeling; surface beta1-integrin activity assays; immunofluorescence; cell migration assays; siRNA knockdown |
Journal of cell science |
Medium |
31076515
|
| 2020 |
Peripheral translation of RAB13 mRNA at cellular protrusions leads to co-translational association of nascent RAB13 with the exchange factor RABIF. This co-translational RAB13-RABIF association at the cell periphery is required for directing RAB13 GTPase activity and promoting efficient cell migration. Preventing RAB13 mRNA localization (without affecting total RAB13 protein levels or membrane association) reduces RAB13 GTPase activation and cell migration efficiency. |
RNA localization perturbation constructs; RABIF co-translational interaction assays; GTPase activity measurements; cell migration assays; ribosome fractionation |
The EMBO journal |
High |
32946136
|
| 2020 |
RAB13 mRNA is targeted to sites of filopodia formation via a 192-nt localisation element. This spatial coupling of mRNA localisation, translation, and protein activity creates a polarised domain of filopodia extension. Genomic excision of this localisation element depolarises filopodia dynamics in motile endothelial cells and induces mispatterning of blood vessels in zebrafish without affecting total RAB13 translation. |
Single-molecule RNA FISH; gene editing (CRISPR); zebrafish live-cell imaging; protrusion-derived RNAseq; filopodia dynamics measurements |
The EMBO journal |
High |
32946121
|
| 2020 |
Rab13 regulates secretion of small extracellular vesicles (sEVs) in mutant KRAS colorectal cancer cells. Rab13 is both a cargo protein packaged into sEVs and a regulator of sEV secretion. Knockdown of Rab13 blocks proliferative and tumorigenic effects of sEVs on recipient cells. |
siRNA knockdown; sEV isolation and characterization; recipient cell proliferation and tumorigenesis assays; Western blot |
Scientific reports |
Medium |
32978434
|
| 2022 |
RNF115 (an E3 ubiquitin ligase) catalyzes K11-linked ubiquitination on Lys46 and Lys58 residues of RAB13. This modification impairs recruitment of GDI1 to RAB13, a prerequisite for RAB reactivation. Knockdown of RAB13 inhibits post-Golgi trafficking of TLRs to the cell surface, and reconstitution of RAB13 with K46/58R mutations (ubiquitination-resistant) in RNF115+/+ cells promotes TLR trafficking from Golgi to cell surface. |
Co-immunoprecipitation; ubiquitination assays; site-directed mutagenesis (K46R, K58R); siRNA knockdown; TLR trafficking assays; subcellular fractionation; GDI1 recruitment assay |
Advanced science |
High |
35343654
|
| 2022 |
Rab13 controls membrane translocation of CXCR1/2 receptors, allowing breast cancer stem cells to interact with tumor-associated macrophages and cancer-associated fibroblasts to establish a supportive CSC niche. Rab13 depletion suppresses stemness and chemoresistance. |
siRNA knockdown; surface CXCR1/2 measurement; co-culture assays; in vivo tumorigenesis assays; flow cytometry |
Cancer research |
Medium |
35395074
|
| 2007 |
Rab13 and JRAB/MICAL-L2 are required for TPA-induced epithelial cell scattering (MDCK cells). During scattering, Rab13 is transiently activated; both Rab13 and JRAB/MICAL-L2 redistribute from cell-cell contact sites to emerging lamellipodial structures. Knockdown of either Rab13 or JRAB/MICAL-L2 suppresses TPA-induced scattering. |
siRNA knockdown; Rab13 GTP-loading assay; immunofluorescence; cell scattering assay |
Oncogene |
Medium |
17891173
|
| 2008 |
RAB13 associates with vinculin and espin (ectoplasmic specialization actin-binding proteins) in the testis, as demonstrated by co-immunoprecipitation and immunofluorescence. RAB13 localizes to the ectoplasmic specialization in Sertoli-germ cell junctions and its level decreases during adjudin-induced ectoplasmic specialization disassembly. |
Co-immunoprecipitation; immunofluorescence; immunohistochemistry; in vivo adjudin model |
Biology of reproduction |
Medium |
19074001
|
| 2013 |
RAB13 knockdown in cultured Sertoli cells increases PKA activity, reinforces occludin and filamentous actin distribution at cell-cell interfaces, and promotes ZO-1–occludin direct interaction—effects that phenocopy testosterone's enhancement of TJ integrity. The effects of Rab13 knockdown on TJ permeability are antagonized by PKA inhibition, establishing a Rab13–PKA axis in Sertoli cell TJ regulation. |
siRNA knockdown in primary cultured Sertoli cells; transepithelial electrical resistance; co-immunoprecipitation; immunofluorescence; PKA activity assay |
Journal of molecular endocrinology |
Medium |
23419316
|
| 2013 |
JRAB/MICAL-L2 in its open conformational state (JRABΔCC mutant) interacts with filamin isoforms (actin cross-linking proteins) as well as actinin-1 and actinin-4. Filamin but not actinin is required for JRAB-induced cell spreading with membrane ruffles. Degradation of filamins by ASB2 inhibits JRAB-induced cell spreading. |
Co-immunoprecipitation; expression of constitutively open/closed JRAB mutants; ASB2-induced filamin degradation; morphological cell spreading analysis |
Genes to cells |
Medium |
23890175
|
| 2013 |
Rab13 and Rab8 both bind to Endospanin-2 (and its homolog Endospanin-1) via the C-terminus of Endospanin-2, as demonstrated by bacterial two-hybrid and colocalization in perinuclear vesicular structures. Rab7, Rab10, Rab11, and Rab32 do not bind Endospanin-2. |
Bacterial two-hybrid screen; co-immunoprecipitation; immunofluorescence colocalization |
FEBS open bio |
Low |
23772379
|
| 2003 |
Rab13 mutants specifically impair cell-surface transport of claudin-1 but not basolateral LDLR or apical p75NTR in fibroblasts, while Rab3B mutants affect LDLR but not claudin-1 or p75NTR. This defines distinct and non-overlapping roles for Rab13 and Rab3B in polarized transport. |
Overexpression of dominant mutant Rabs; cell-surface transport assays for specific cargo proteins in fibroblasts |
Biochemical and biophysical research communications |
Medium |
12901864
|
| 2017 |
Active Rab13 promotes autophagy in vascular endothelial cells by functionally interacting with Grb2, leading to AMPK activation and mTOR inhibition. Co-immunoprecipitation assays showed Rab13 promotes Rab13–Grb2 interaction; Grb2 knockdown suppresses Rab13-induced autophagy. |
Overexpression of active/inactive Rab13; siRNA knockdown of Grb2; co-immunoprecipitation; immunofluorescence; autophagy quantification; mTOR/AMPK phosphorylation assays |
Biochimica et biophysica acta. Molecular cell research |
Medium |
28087344
|
| 2024 |
Parkin (RBR E3 ubiquitin ligase) ubiquitinates RAB13 in cells. This was identified in an orthogonal ubiquitin transfer (OUT) screen and confirmed by reconstituted ubiquitination reactions in vitro and in cells. Mitophagy stimulation enhanced Parkin-mediated ubiquitination of RAB13. |
Orthogonal ubiquitin transfer (OUT) cascade; proteomics; in vitro reconstituted ubiquitination assay; cell-based ubiquitination assay |
bioRxivpreprint |
Medium |
|