The Stahlman Cardiovascular Research Laboratories, Program for Developmental Biology, and Department of Medicine, Vanderbilt University, Medical Center, Nashville, TN 37232, USA.
EMBO J. 2010 Feb 3;29(3):532-45. doi: 10.1038/emboj.2009.379. Epub 2010 Jan 7.
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.
血管/心外膜物质（Bves）是一种跨膜蛋白，通过未知机制影响细胞黏附和运动。我们发现 Bves 可直接与 VAMP3 相互作用，VAMP3 是一种 SNARE 蛋白，可促进囊泡运输，并特异性地回收转铁蛋白和β1-整合素。两项独立的实验证明，表达突变形式 Bves 的细胞在这些分子的回收中受到严重损害，这种表型与 VAMP3 功能的破坏一致。利用非洲爪蟾中的 Morpholino 敲低，我们证明 Bves 功能的消除特异性抑制转铁蛋白受体的回收，并导致以前报道的与整合素依赖性细胞运动受损相关的原肠胚形成缺陷。对 Bves 耗尽的原代和培养细胞的轨迹分析显示，在纤维连接蛋白上细胞铺展和黏附严重受损，表明整合素介导的黏附受到破坏。总之，这些数据表明 Bves 与 VAMP3 相互作用，可促进体外和早期发育过程中受体的回收。因此，本研究确立了 Bves 在囊泡运输中的新作用，并揭示了一种新的、广泛应用的调节 SNARE 蛋白功能的机制。
