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The Journal of cell biology
11 04, 2019;218 (11): 3812-3826.

Arf6 regulates RhoB subcellular localization to control cancer cell invasion.

Kossay Zaoui, Charles V Rajadurai, Stéphanie Duhamel, Morag Park
Author Information
  1. Kossay Zaoui: Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
  2. Charles V Rajadurai: Department of Biochemistry, McGill University, Montreal, Quebec, Canada. ORCID
  3. Stéphanie Duhamel: Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec, Canada stephanie.duhamel@mcgill.ca. ORCID
  4. Morag Park: Department of Biochemistry, McGill University, Montreal, Quebec, Canada morag.park@mcgill.ca. ORCID
PMID: 31591185 DOI: 10.1083/jcb.201806111

Abstract

The ADP-ribosylation factor 6 (Arf6) is a small GTPase that regulates endocytic recycling processes in concert with various effectors. Arf6 controls cytoskeletal organization and membrane trafficking; however, the detailed mechanisms of regulation remain poorly understood. Here, we report that Arf6 forms a complex with RhoB. The interaction between RhoB.and Arf6 is mediated by the GCI (glycine, cysteine, and isoleucine) residues (188-190) of RhoB. Specific targeting of Arf6 to plasma membrane or mitochondrial membranes promotes recruitment and colocalization of RhoB.to these membrane microdomains. Arf6 depletion promotes the loss of RhoB.from endosomal membranes and leads to RhoB.degradation through an endolysosomal pathway. This results in defective actin and focal adhesion dynamics and increased 3D cell migration upon activation of the Met receptor tyrosine kinase. Our findings identify a novel regulatory mechanism for RhoB.localization and stability by Arf6 and establish the strict requirement of Arf6 for RhoB.specific subcellular targeting to endosomes and biological functions.

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Grants

  1. 242529/CIHR

MeSH Term

ADP-Ribosylation Factor 6
ADP-Ribosylation Factors
Breast Neoplasms
Cell Proliferation
Endosomes
Female
HeLa Cells
Humans
Tumor Cells, Cultured
Uterine Cervical Neoplasms
rhoB GTP-Binding Protein

Chemicals

ADP-Ribosylation Factor 6
RHOB protein, human
ADP-Ribosylation Factors
ARF6 protein, human
rhoB GTP-Binding Protein
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 6

Word Cloud

Created with Highcharts 10.0.0Arf6RhoBmembraneregulatestargetingmembranespromotescelllocalizationsubcellularADP-ribosylationfactor6smallGTPaseendocyticrecyclingprocessesconcertvariouseffectorscontrolscytoskeletalorganizationtraffickinghoweverdetailedmechanismsregulationremainpoorlyunderstoodreportformscomplexinteractionmediatedGCIglycinecysteineisoleucineresidues188-190Specificplasmamitochondrialrecruitmentcolocalizationmicrodomainsdepletionlossendosomalleadsdegradationendolysosomalpathwayresultsdefectiveactinfocaladhesiondynamicsincreased3DmigrationuponactivationMetreceptortyrosinekinasefindingsidentifynovelregulatorymechanismstabilityestablishstrictrequirementRhoB-specificendosomesbiologicalfunctionscontrolcancerinvasion

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