| 2005 |
Wnt11 controls tissue morphogenesis during zebrafish gastrulation by modulating E-cadherin-mediated cell cohesion through Rab5c; blocking Rab5c activity phenocopied wnt11 mutants and enhancing Rab5c activity rescued the mutant phenotype, establishing Rab5c as a downstream mediator of Wnt11 signaling that regulates E-cadherin endocytosis. |
Genetic epistasis in zebrafish (dominant-negative/constitutively-active Rab5c injection, rescue experiments in slb/wnt11 mutants), E-cadherin endocytosis assays |
Developmental cell |
High |
16198297
|
| 1999 |
The three Rab5 isoforms (Rab5a, Rab5b, Rab5c) are differentially phosphorylated in vitro: Rab5a is efficiently phosphorylated by ERK1 but not ERK2; Rab5b is preferentially phosphorylated by Cdc2 kinase at Ser-123; Rab5c was not efficiently phosphorylated by these same kinases, establishing isoform-specific post-translational regulation. |
In vitro kinase phosphorylation assays with ERK1, ERK2, and Cdc2 kinase |
FEBS letters |
Medium |
10403367
|
| 2012 |
GTP-Rab5c binds directly to AMAP1, and EGFR-stimulated activation of Rab5c is necessary to promote the intracellular association of AMAP1 and PRKD2, forming a complex that recycles β1 integrins (e.g., α3β1) to promote breast cancer cell invasion. |
Co-immunoprecipitation, direct binding assays, siRNA knockdown of Rab5c with invasion/recycling readouts |
The Journal of cell biology |
High |
22734003
|
| 2014 |
Rab5C, but not Rab5A or Rab5B, is selectively required for EGF-stimulated Rac1 activation and cell motility; depletion of Rab5C suppressed EGF-induced Rac1 activity, reduced peripheral Rac1 localization, decreased Akt phosphorylation, reduced focal adhesion formation, and impaired directional cell migration. |
siRNA isoform-specific knockdown, Rac1 GTP pull-down assays, scratch wound and Transwell migration assays, micro-patterned cell imaging, phospho-Akt western blot |
PloS one |
High |
24587345
|
| 2018 |
Rab5C and EEA1 in the early endosomal pathway are rate-limiting regulators of antisense oligonucleotide (PS-ASO) trafficking and endosomal escape following Stabilin receptor-mediated internalization; modulating their expression altered the efficiency of ASO escape from endolysosomal compartments. |
Modulation of Rab5C expression (knockdown/overexpression) in cells, tracking of PS-ASO trafficking and endosomal escape |
Nucleic acid therapeutics |
Medium |
29437530
|
| 2019 |
Rab5c is a key component of the endosomal recycling machinery for CD93 in endothelial cells; Rab5c-containing endosomal compartments harbor a complex of CD93, Multimerin-2, and active β1 integrin that is recycled back to the basolaterally-polarized cell surface by clathrin-independent endocytosis, and Rab5c silencing impairs CD93 recycling and cell migration. |
Gene silencing (siRNA), fluorescence confocal microscopy, co-immunoprecipitation, scratch assay for migration, flow cytometry |
Cell communication and signaling : CCS |
Medium |
31138217
|
| 2019 |
Rab5c modulates EGFR internalization in rectal cancer cells in response to irradiation, and this modulation affects EGFR nuclear relocalization, which in turn regulates expression of DNA repair proteins Ku70 and Ku80 to confer radiotherapy resistance. |
Rab5c knockdown/overexpression in irradiated rectal adenocarcinoma cell lines, EGFR internalization assays, western blot for Ku70/Ku80, radioresistance assays |
Journal of molecular medicine (Berlin, Germany) |
Medium |
30968159
|
| 2020 |
Rab5c is essential for hematopoietic stem and progenitor cell (HSPC) specification in zebrafish via endocytic trafficking of Notch ligands and receptor; additionally, Rab5c interacts with Appl1 in endosomes to activate AKT signaling required for hemogenic endothelium survival, and Rab5c overactivation causes excessive endolysosomal Notch degradation and HSPC defects. |
Zebrafish rab5c morpholino knockdown and overexpression, co-immunoprecipitation of Rab5c with Appl1, endocytic trafficking assays of Notch components, AKT phosphorylation readouts |
PLoS biology |
High |
32275659
|
| 2014 |
RAB5C is a direct target of miR-509; enforced miR-509 expression reduced RAB5C mRNA and protein in B-ALL cells, and knockdown of RAB5C alone recapitulated the growth-inhibitory and pro-apoptotic effects of miR-509; co-expression of RAB5C ORF (without 3'UTR) blocked miR-509-mediated growth inhibition. |
miR-509 overexpression, RAB5C shRNA knockdown, rescue by RAB5C ORF re-expression, luciferase reporter assay for direct targeting, flow cytometry for proliferation/apoptosis |
PloS one |
Medium |
25368993
|
| 2014 |
RAB5C physically interacts with TPD52 (Tumor Protein D52); this interaction was identified by yeast two-hybrid screening and confirmed by pull-down assays, with domain mapping identifying a novel binding region on TPD52. |
Yeast two-hybrid screening, pull-down assays, interaction domain mapping |
Molecular biology reports |
Low |
24604726
|
| 2021 |
TBC1D16, a TBC domain-containing GAP protein, targets Rab5C to suppress prototype foamy virus (PFV) replication; the conserved arginine finger and glutamine residues R494 and Q531 in the TBC domain are essential for this inhibitory function, and TBC1D16 promotes IFN-β production. |
TBC1D16 overexpression/silencing in PFV-infected cells, mutagenesis of TBC domain catalytic residues (R494A, Q531A), IFN-β reporter assays |
Frontiers in immunology |
Medium |
34367131
|
| 2022 |
Piezo1 recruits and physically interacts with Rab5c to activate TGF-β signaling, thereby promoting HCC progression and EMT; knockdown of Piezo1 impaired this complex formation and reduced TGF-β pathway activation. |
Co-immunoprecipitation, immunofluorescence colocalization, Piezo1 knockdown with TGF-β signaling readouts, in vitro and in vivo tumor models |
Cancer cell international |
Medium |
35461277
|
| 2022 |
HuR RNA-binding protein binds the 3'UTR of RAB5C mRNA to stabilize it, maintaining RAB5C protein levels; HuR shRNA knockdown decreased RAB5C mRNA and protein, and suppression of RAB5C reduced breast cancer cell proliferation. |
RNA immunoprecipitation (RIP) of HuR-RAB5C mRNA, shRNA knockdown of HuR, mRNA stability assays, colony formation and MTT assays |
Cell biology international |
Medium |
36480789
|
| 2023 |
Heterozygous de novo missense variants in RAB5C cause macrocephaly and developmental delay; biochemical studies showed the variants increased nucleotide exchange rate, attenuated responsivity to guanine exchange factors, and had heterogeneous effects on effector protein interactions; two variants acted through a dominant-negative mechanism; C. elegans and zebrafish models confirmed in vivo disruption of the endocytic pathway. |
In vitro nucleotide exchange assays, GEF responsivity assays, effector binding assays, C. elegans in vivo endocytic pathway assays, zebrafish embryo expression studies |
Human molecular genetics |
High |
37552066
|
| 2024 |
Rab5c promotes RSV and ADV replication via autophagy rather than endocytosis; activated Rab5c upregulates LC3-II protein expression by interacting with Beclin1, inducing autophagy that facilitates viral replication in respiratory epithelial cells and in Rab5c-overexpressing mice. |
Rab5c overexpression/knockdown in A549 cells and transgenic mice, co-immunoprecipitation of Rab5c with Beclin1, LC3-II western blot, viral replication assays |
Virus research |
Medium |
38242290
|
| 2025 |
RAB5c regulates phagosome recruitment of complexes required for PI(3)P and ROS generation during LC3-associated phagocytosis (LAP); specifically, RAB5c facilitates phagosome translocation of the V-ATPase transmembrane core, which enables ATG16L1 binding and consequent LC3 conjugation to phagosomes; RAB5c depletion impaired macrophage elimination of Aspergillus fumigatus and disruption of the V-ATPase-ATG16L1 axis increased susceptibility in vivo. |
RAB5c knockdown/depletion in macrophages, phagosome fractionation, V-ATPase and ATG16L1 recruitment assays, LC3 conjugation assays, in vivo Aspergillus fumigatus infection model |
Science advances |
High |
42102192
|
| 2024 |
Parkin E3 ubiquitin ligase ubiquitinates RAB5C (along with other Rab GTPases); this was identified by orthogonal ubiquitin transfer (OUT) proteomics and confirmed by reconstituted in vitro ubiquitination reactions, and Parkin-mediated ubiquitination of Rab proteins was enhanced upon mitophagy stimulation. |
Orthogonal ubiquitin transfer (OUT) cascade proteomics, in vitro reconstituted ubiquitination assay, mitophagy stimulation experiments |
bioRxivpreprint |
Medium |
bio_10.1101_2024.09.14.613079
|
| 2026 |
RAB5C regulates VWF exocytosis from endothelial cells; RAB5C silencing decreased VWF release after histamine stimulation whereas constitutively active RAB5C increased it; proximity labeling and mass spectrometry identified SNAP29 (a SNARE-associated protein) as a key RAB5C interactor mediating this effect on vesicle fusion and VWF secretion. |
RAB5C silencing/overexpression in HUVECs, ELISA for VWF release, proximity labeling (BioID) + mass spectrometry for interactome, constitutively active and dominant negative RAB5C constructs |
Arteriosclerosis, thrombosis, and vascular biology |
High |
41537263
|
| 2026 |
Rab5c-dependent endocytosis of AMPA receptor subunits GluA1 and GluA2 mediates developmental synaptic downscaling in Xenopus tadpoles; prolonged visual experience accelerated this Rab5c-dependent AMPAR endocytosis, reducing mEPSC amplitudes, and the effect was reversible. |
Rab5c manipulation in Xenopus laevis tadpoles, electrophysiology (mEPSC recordings), AMPAR subunit trafficking assays, pharmacological and genetic inhibition of Rab5c |
Communications biology |
Medium |
41507541
|
| 1996 |
The human RABL gene (now RAB5C) encodes a 216 amino acid small GTP-binding protein with 86% amino acid identity to the RAB5 subfamily; it is expressed ubiquitously in all human tissues examined and maps to chromosome band 17q21.2 by FISH. |
cDNA cloning from human fetal lung library, sequence analysis, fluorescence in situ hybridization (FISH) for chromosomal mapping, northern blot for tissue expression |
Cytogenetics and cell genetics |
Medium |
8646882
|