Regulation of integrin activity during xenopus development

运动能力是细胞的基本属性。细胞要改变位置，它必须粘附在细胞外环境中并在细胞外环境中移位。整合素是一类在细胞运动中具有活性的细胞粘附分子家族，整合素粘附的转换对于细胞有效运动是重要的。整合素周转的机制知之甚少，但需要来自细胞内外的信号。了解这些信号以及它们是如何被处理的，是了解细胞运动的关键，这些细胞运动对胚胎发育、伤口愈合以及疾病进展至关重要。在我的研究项目中，我研究细胞如何解释和响应它们的直接环境。更重要的是，我还研究细胞本身如何创造或修改它们的环境，改变它们未来的行为。我提出了三个目标，解决这个整体研究计划的各个方面。首先，我将研究生长因子如何通过募集胞质蛋白kermit 2促进迁移细胞中整合素α 5 β 1的周转。其次，我将研究整合素α 5 β 1如何通过蛋白质复合物（PIP复合物）传递细胞内信号，该蛋白质复合物在连接到纤连蛋白后促进细胞迁移。最后，我将分离PIP复合物的组成部分，并询问这些组成部分对整合素信号传导的单独贡献。我解决这些目标，使用分子和先进的成像技术，以获得独特的信息，在一个细胞内的分子动力学的背景下，多细胞组织。这些项目将共同为复杂组织中细胞粘附的调节提供新的解释。

The ability to move is a basic property of cells. For a cell to change position it must adhere to and translocate on the extra-cellular environment. The integrins are a family of cell adhesion molecules that are active in cell movements, and the turnover of integrin adhesion is important for cells to move effectively. The mechanisms by which integrins turnover is poorly understood, but requires signals that stem from both outside and within cells. Understanding these signals and how they are processed is key to understanding cell movements that are central to embryonic development, wound healing as well as disease progression. In my research program, I investigate how cells interpret and respond to their immediate environment. More importantly, I also study how cells themselves create or modify their environment altering their future behavior. I propose three objectives that address aspects of this overall research program. First I will investigate how growth factors promote integrin a5ß1 turnover in migrating cells through the recruitment of the cytoplasmic protein kermit2. Second, I will look at how integrin a5ß1 transmits intracellular signals through a complex of proteins (PIP complex) that promote cell migration following ligation to fibronectin. Finally, I will isolate components of the PIP complex and ask what is the individual contribution of these components to integrin signaling. I address these objectives using both molecular and advanced imaging techniques to obtain unique information on molecular dynamics within a cell in the context of multi-cellular tissues. Together these projects will provide novel interpretations of how cell adhesion is modulated in complex tissues.