Cell polarization is fundamentally important for many physiological processes such as embryonic development, cell motility and cell differentiation. Elucidation of the mechanism underlying cell polarity establishment is important for understanding developmental abnormalities and diseases such as invasive tumor and arteriosclerosis. Identification of the molecules that are specialized in cell polarity generation may reveal novo therapeutic targets for these diseases. In addition, how cells break symmetry and establish a polarity is a profound problem in cell biology. Understanding cell's intrinsic ability to polarize may lead to fundamental insights into the physical principles that govern cellular organization and morphogenesis. A key regulator of cell polarity in many eukaryotic cell types is the Rho-family GTPase Cdc42. During cell polarization, Cdc42 is activated in a localized manner and induces downstream events, most importantly, the generation of localized actin cytoskeletal elements. The goal of this proposal is to understand how Cdc42 induces polarized polymerization of actin filaments. We will continue our ongoing work studying how actin filaments are nucleated at cell cortex and how Cdc42 defines the site of actin nucleation during cell polarization. We will also investigate the mechanism by which the activated form of Cdc42 drives the initial breakage of cell symmetry.
The specific aims are: 1) Biochemical characterization of the Bee1/Vrp1/myosin-I complex;2) Studying the regulation of the Bee1/Vrp1/myosin-I complex during cell polarization;3) Understanding the mechanism by which the Arp2/3 complex nucleate actin polymerization;4) Investigating the Intrinsic mechanism that drives cell polarity generation.
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