Regulation of formins and cell polarity

福尔明和细胞极性的调节

• 批准号: 9028874
• 负责人: Bruce L Goode
• 金额: $ 42.48万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9028874
• 关键词: Actins; Address; Alzheimer' s Disease; Architecture; Binding; Biochemical; Biochemistry; CLIP-170 gene; Cell Polarity; Cell physiology; Cells; Characteristics; Colorectal Cancer; Complex; Cytokinesis; Cytoskeleton; Disease; Endocytosis; Ensure; Event; F-Actin; Family; Feedback; Fibroblasts; Filament; Foundations; Funding; Genetic; Goals; Grant; Growth; Hodgkin Disease; Homologous Gene; Human; Huntington Disease; Image; In Vitro; Kinesin; Length; Life; Ligands; Link; Mammalian Cell; Mammals; Mediating; Microfilaments; Modeling; Molecular; Morphogenesis; Mutation; Myosin ATPase; Organelles; Parkinson Disease; Physiological; Polymers; Protein Family; Protein Isoforms; Proteins; Regulation; Research; Role; Saccharomycetales; Secretory Vesicles; Site; Speed; System; Testing; Thick; Tissues; Total Internal Reflection Fluorescent; Tropomyosin; Work; Yeasts; base; cell growth; cell motility; combinatorial; design; genetic approach; human disease; in vivo; insight; live cell imaging; macrophage; novel; polarized cell; profilin; public health relevance; single molecule

 DESCRIPTION (provided by applicant): The goal of this research is to determine how the assembly dynamics and architecture of the actin cytoskeleton are controlled by formins and the cellular mechanisms regulating their activities. We are studying this question in budding yeast, where formins assemble actin cables of a characteristic length, architecture, and dynamics required for polarized cell growth. Further, we extend this work to mammalian formin regulation. The proposal focuses on several new multi-component mechanisms discovered during the previous funding cycle, which control formin-mediated actin nucleation, or the duration and speed of formin-mediated actin filament elongation events. The project combines genetics, live- cell imaging, biochemistry, and novel multi-wavelength single molecule TIRF microscopy. The Aims are: (1) Test the hypothesis that formin-mediated actin cable nucleation is spatially and temporally controlled by the combinatorial effects of Bud6, profilin, Tpm1, and Tpm2; (2) Test the hypothesis that actin cable length, velocity, and architecture are controlled by dynamic interplay at filament barbed ends involving formins, Bud14-Kel1-Kel2 complex, capping protein, and Smy1; and (3) Test the hypothesis that human CLIP-170 interacts with mDia1 to form a novel barbed end- tracking complex that supports ultrafast actin filament elongation in vitro and in vivo.