Identification of a novel Bves function: regulation of vesicular transport

HA Hager, RJ Roberts, EE Cross… - The EMBO …, 2010 - embopress.org
HA Hager, RJ Roberts, EE Cross, V Proux‐Gillardeaux, DM Bader
The EMBO Journal, 2010embopress.org
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 β‐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 …
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 β‐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.
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