Hevin Regulation of Cell Migration

描述（由申请人提供）：细胞外基质（ECM）结构是细胞行为的已知决定因素，进而受来自其相邻细胞的信号调节。基质细胞蛋白如hevin通过充当适配器在调节细胞/ECM通信和ECM结构中起重要作用，因此是许多病理如肿瘤生长及其相关血管生成的关键调节剂。这个提议的假设是hevin通过诱导允许迁移的粘附状态来作为细胞迁移的调节剂。解决这一假说的具体目标集中在阐明一个或多个赫文功能的机制。首先，我们将研究hevin/胶原I相互作用在脱粘中的作用，其次，我们将研究hevin诱导的粘着斑解体的机制。为了解决第一个具体的目标，我们将评估hevin/胶原蛋白I结合及其对胶原纤维的合成，结构和相互作用与α 2 β 1-整联蛋白在真皮成纤维细胞。为了解决第二个具体的目标，我们将调查参与调节局灶性粘附拆卸和细胞迁移的hevin在牛主动脉内皮细胞和真皮成纤维细胞的信号通路。

DESCRIPTION (provided by applicant): Extracellular matrix (ECM) structure is a known determinant of cell behavior and is in turn regulated by signals from its adjacent cells. Matricellular proteins such as hevin play an important role in regulating cell/ECM communication and ECM structure by acting as adapters, and therefore are critical regulators of numerous pathologies such as tumor growth and its associated angiogenesis. The hypothesis of this proposal is that hevin functions as a regulator of cell migration by inducing a state of adhesion permissive for migration. The specific aims geared to address this hypothesis are focused on elucidating one or more of the mechanisms through which hevin functions. First, we will investigate the role of the hevin/collagen I interaction in deadhesion, and second, we will examine the mechanism of hevin-induced focal adhesion disassembly. To address the first specific aim, we will evaluate hevin/collagen I binding and its effect on collagen fibril synthesis, structure, and interaction with alpha2beta1-integrin in dermal fibroblasts. To address the second specific aim, we will investigate the signaling pathways involved in regulating focal adhesion disassembly and cell migration by hevin in bovine aortic endothelial cells and dermal fibroblasts.