UBC Theses and Dissertations
Analysis of integrin turnover in Drosophila myotendinous junctions Yuan, Lin
Integrins are essential mediators of cell-ECM adhesion and they are, therefore, important to animal viability. Integrin-mediated transient (short-term) cell adhesion underlies dynamic processes such as cell migration while integrin-mediated stable (long-term) cell adhesion is essential for maintaining tissue architecture. Ongoing adhesion complex turnover is essential for transient cell adhesion, but it is unknown whether turnover is also required for maintenance of long-term adhesion. Fluorescence Recovery After Photobleaching (FRAP) was used to analyze the dynamics of the Integrin Adhesion Complex (IAC) in a model for long-term cell-ECM adhesion, Myotendinous Junctions (MTJs), in fly embryos and larvae. It was found that the IAC undergoes turnover in the MTJs and that this process is mediated by clathrin-dependent endocytosis but not lateral diffusion. Moreover, the small GTPase Rab5 can regulate the proportion of IAC components that undergo turnover and altering Rab5 activity weakened MTJs such that it leads to muscle attachment defects. In addition, growth of the MTJs was concomitant with a decrease in the proportion of IAC components undergoing turnover and it is possible that this growth-dependent decrease is regulated by the mechanical tension exerted on MTJs by muscle contraction. Experiments using mutations that result in increased mechanical tension exhibited lower IAC turnover. In contrast, mutations that lower mechanical tension exhibited higher IAC turnover with the exception of integrins. Therefore, we propose that IAC turnover is regulated during development by mechanical tension in long-term cell-ECM adhesions to allow normal tissue growth and maintenance.
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