Regulation of cell adhesion during Xenopus morphogenesis

移动的能力是细胞的基本属性。为了让细胞改变位置，它必须附着在细胞外环境中并在细胞外环境中转移。整合素是一类活跃在细胞运动中的细胞黏附分子家族，整合素黏附的调节对细胞的有效运动具有重要意义。整合素的调控机制知之甚少，但已知需要来自细胞外和细胞内的信号。了解这些信号以及它们是如何产生和处理的，对于了解对胚胎发育、伤口愈合以及疾病进展至关重要的细胞运动是关键。在我的研究计划中，我调查了细胞如何解释和回应他们周围的环境。更重要的是，我还研究了细胞本身如何创造或修改它们的环境，从而改变它们未来的行为。我将研究生长因子如何通过细胞质蛋白kermit2的募集来促进整合素受体在迁移细胞中的周转。其次，我将研究整合素如何通过蛋白质复合体(PIP复合体)传递细胞内信号，以及这些信号如何影响其他形式的细胞黏附。最后，我将分离PIP复合体的组件，并询问这些组件对整合素信号的单独贡献是什么。我使用分子和先进的成像技术来解决这些目标，以在多细胞组织的背景下获得关于细胞内分子动力学的独特信息。总之，这些项目将为复杂组织中细胞黏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 regulation of integrin adhesion is important for cells to move effectively. The mechanisms by which integrins are regulated is poorly understood, but it is known to require signals that stem from both outside and within cells. Understanding these signals and how they are generated and 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 will investigate how growth factors promote integrin receptor turnover in migrating cells through the recruitment of the cytoplasmic protein kermit2. Second, I will look at how integrins transmit intracellular signals through a complex of proteins (PIP complex), and how those signals affect other forms of cell adhesion. 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.