The Role of SNARE-mediated Membrane Traffic in Cell-ECM Adhesion

多细胞生命取决于组织内细胞支持与其他细胞和细胞外基质（ECM）动态相互作用的能力。近几十年来，我们对细胞-ECM相互作用（包括细胞粘附、迁移和侵袭）的理解有了很大的进展，但对调节这些相互作用的分子机制知之甚少。目前的细胞粘附模型表明，细胞和ECM之间的相互作用主要是由粘着斑（FA）介导的，粘着斑是一种蛋白质复合物，作为ECM和细胞骨架之间的连接位点，并作为信息传递进出细胞的局部点。 我实验室的NSERC资助的研究是第一批确定细胞内物质的运输如何在细胞与ECM结合时有助于FA的形成和功能的研究之一。凭借我们所获得的知识和我们开发的模型系统，我们现在处于独特的地位，以进一步了解细胞-ECM粘附是如何控制的，以及它在体内许多组织的正常功能和许多疾病状态中所起的作用。 拟开展的研究包括三个目标：（1）表征粘着斑组分的细胞内转运，（2）确定SNARE蛋白如何促进粘着斑形成，（3）确定控制细胞粘附的SNARE功能调节剂。 计划中的研究将有助于确定细胞内运输有助于细胞与环境之间动态相互作用的分子机制。 这是细胞生物学中一个广泛关注的领域，对许多生物和医学领域都有影响，也为培养高素质人才提供了极好的机会。

Multicellular life depends on the capacity of cells within tissues to support dynamic interactions with other cells and with the extracellular matrix (ECM). In recent decades, there have been great advances in our understanding of cell-ECM interactions (including cell adhesion, migration and invasion), yet little is known of the molecular mechanisms that regulate these interactions. Current models of cell adhesion suggest that interactions between cells and ECM are primarily mediated by focal adhesions (FAs), protein complexes that act as sites of connection between the ECM and the cell cytoskeleton and serve as local points of information transfer into and out of cells. NSERC-funded studies from my laboratory are among the first to establish how the transport of material within cells contributes to the formation and function of FAs while cells bind to the ECM. With the knowledge we have gained and the model system we have developed, we are now uniquely positioned to further our understanding of how cell-ECM adhesion is controlled and the role this plays in both the normal function of many tissues within the body and in many disease states. The proposed research consists of three aims: (1) To characterize the intracellular transport of focal adhesion components, (2) To define how SNARE proteins contribute to focal adhesion formation, and (3) To identify regulators of SNARE function that control cell adhesion. The planned studies will help to define the molecular mechanisms by which transport within cells contributes to the dynamic interactions between cells and their environment. This is an area of broad interest in cell biology, with ramifications for many biological and medical fields, that also provides excellent opportunities for the training of highly qualified personnel.