Identification of a novel Bves function: regulation of vesicular transport.
Blood vessel/epicardial substance (Bves) is a transmembrane protein that influences cell adhesion and motility through unknown mechanisms. We have discovered that Bves directly interacts with VAMP3, a SNARE protein that facilitates vesicular transport and specifically recycles transferrin and beta-1-integrin. Two independent assays document that cells expressing a mutated form of Bves are severely impaired in the recycling of these molecules, a phenotype consistent with disruption of VAMP3 function. Using Morpholino knockdown in Xenopus laevis, we demonstrate that elimination of Bves function specifically inhibits transferrin receptor recycling, and results in gastrulation defects previously reported with impaired integrin-dependent cell movements. Kymographic analysis of Bves-depleted primary and cultured cells reveals severe impairment of cell spreading and adhesion on fibronectin, indicative of disruption of integrin-mediated adhesion. Taken together, these data demonstrate that Bves interacts with VAMP3 and facilitates receptor recycling both in vitro and during early development. Thus, this study establishes a newly identified role for Bves in vesicular transport and reveals a novel, broadly applied mechanism governing SNARE protein function.
Hager
Hillary A
HA
The Stahlman Cardiovascular Research Laboratories, Program for Developmental Biology, and Department of Medicine, Vanderbilt University, Medical Center, Nashville, TN 37232, USA.
Roberts
Ryan J
RJ
Cross
Emily E
EE
Proux-Gillardeaux
Véronique
V
Bader
David M
DM
D000818:Animals; D001692:Biological Transport / Q000235:genetics; D019556:COS Cells; D002448:Cell Adhesion / Q000235:genetics; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004285:Dogs; D004625:Embryo, Nonmammalian; D019012:Integrin beta1 / Q000378:metabolism / Q000502:physiology; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050505:Mutant Proteins / Q000378:metabolism / Q000502:physiology; D014018:Tissue Distribution; D014168:Transferrin / Q000378:metabolism; D022161:Transport Vesicles / Q000235:genetics / Q000378:metabolism*; D051040:Vesicle-Associated Membrane Protein 3 / Q000378:metabolism / Q000502:physiology; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014982:Xenopus laevis
C470297:Bves protein, Xenopus; D019012:Integrin beta1; D009124:Muscle Proteins; D050505:Mutant Proteins; D014168:Transferrin; D051040:Vesicle-Associated Membrane Protein 3; D029867:Xenopus Proteins