PROTEIN INTERACTIONS REGULATING CELL MOTILITY

描述：(改编自应用程序)这项工作的长期目标是 了解定向细胞运动的结构和生化基础。 许多细胞有能力移动或改变它们的形状以响应 外部信号。在发育过程中发生的这种运动对 反应和侵袭性肿瘤的形成是由肌动蛋白的重塑介导的。 细胞骨架。为了在空间和时间上发生精确的运动，外部 信号必须被解释并用来确定细胞的极性。肌动蛋白 聚合必须专门针对细胞的前沿，在 它能为薄膜突出提供机械前推力。一类人 接头蛋白，包括使能(Ena)、血管扩张剂刺激蛋白 (VASP)和Wiscott-Aldrich综合征蛋白(WASP)在 控制肌动蛋白聚合。这些蛋白质定位于潜在的前导 通过与上游信号蛋白相互作用的边缘位置。随后，他们 被认为是招募肌动蛋白下游成分的支架 聚合设备。 林博士选择将重点放在这些接头蛋白及其相互作用上 以了解它们如何本地化，以及它们如何充当切换到 激活肌动蛋白聚合。他的大部分努力将指向一个 在这些蛋白质中发现了保守的识别模块，称为激活的Vasp 同源1(EVH1)结构域。EVH1结构域在初始阶段起着核心作用 瞄准目标。他剩下的工作将致力于了解 这些蛋白质随后激活肌动蛋白聚合。他将使用一个 生物物理、结构和细胞生物学方法的结合 实现以下具体目标： (1)阐明激活的Vasp同源1(EVH1)结构域的机制 特异性识别受体中发现的富含脯氨酸的基序； (2)确定EVH1域是否是通用双识别模块，可以 结合磷脂和多肽； (3)确定EVH1结构域在靶向性和极性中的作用 体内建立； (4)阐明了结构和能量基础的转换行为。 神经元WASP。

Description: (Adapted from the application) The long term goal of this work is to understand the structural and biochemical basis of directed cell movement. Many cells have the ability to move or alter their shapes in response to external signals. Such movements, which occur during development, immune response, and invasive tumor formation, are mediated by remodeling of the actin cytoskeleton. For spatially and temporally precise movements to occur, external signals must be interpreted and used to establish cell polarity. Actin polymerization must be specifically targeted to the cell's leading edge where it can provide the mechanical forward force for membrane protrusion. A class of adapter proteins, which include Enabled (Ena), vasodilator stimulated protein (VASP) and Wiscott-Aldrich Syndrome Protein (WASP), plays a central role in controlling actin polymerization. These proteins localize to potential leading edge sites via interactions with upstream signaling proteins. Subsequently they are thought to act as scaffolds to recruit downstream components of the actin polymerization machinery. Dr. Lim has chosen to focus on these adapter proteins and their interactions in order to understand how they are localized and how they act as switches to activate actin polymerization. Much of his effort will be directed towards a conserved recognition module found in these proteins, known as the Enabled VASP Homology 1 (EVH1) domain. EVH1 domains play a central role in initial targeting. The remainder of his effort will be directed at understanding how these proteins subsequently activate actin polymerization. He will use a combination of biophysical, structural, and cell biological approaches to address the following specific aims: (1) Elucidate the mechanism by which the Enabled VASP Homology 1 (EVH1) domain specifically recognizes proline-rich motifs found in receptors; (2) Determine if EVH1 domains are general dual recognition modules that can bind both phospholipids and peptides; (3) Determine the role of the EVH1 domain in targeting and polarity establishment in vivo; (4) Elucidate the structural and energetic basis of switching behavior in neuronal WASP.