Cell polarization is important for such physiological processes as embryonic development, cell motility and cell differentiation. How cells break symmetry and establish polarity is a profound question in cell biology, an answer to which is likely to bring fundamental insights into the physical principles that govern cellular organization and morphogenesis. From a medical perspective, loss of polarity is a critical step in the development of several devastating diseases, such as cancers of epithelial origin and polycystic kidney disease. Elucidation of the mechanisms that control cell polarity is important for understanding the development of these diseases and could bring new ideas and approaches to effective therapy. An important and conserved regulator of cell polarity in eukaryotes is the Rho-family GTPase - Cdc42. Recent work in the budding yeast Saccharomyces cerevisiae has demonstrated that the establishment of cell polarity is intrinsically driven by two coupled positive feedback loops: one involving actin assembly and actin-based transport, and the other independent of actin but requiring the adaptor protein Bem1 - which binds both Cdc42 and the Cdc42 GEF, Cdc24. Coupling these two feedback loops results in robust and temporally precise cell polarization. The polarized state is dynamic and maintained through balancing the flux of three mechanisms: diffusion, recycling and targeting. Based on this framework, we propose three specific aims to further elucidate the mechanistic details in the control of cell polarization: 1) To understand the Bem1-dependent, actin-independent mechanism of cell polarization. 2) To elucidating the mechanism of Cdc42 recycling during cell polarization. 3) To investigating the dynamic organization of the polar cortex through genome-wide FRAP analysis of polar cap components.
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