Regulation of integrin activity during xenopus development

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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.