Positioning the Plane of Cell Division during Cytokinesis

在细胞分裂过程中定位细胞分裂平面

• 批准号: 8860190
• 负责人: Michael A Glotzer
• 金额: $ 31.04万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8860190
• 关键词: Biochemical Genetics; Cell division; Cell membrane; Cell physiology; Cells; Complex; Cytokinesis; Cytoskeleton; Embryo; Environment; Event; Excision; F-Actin; Family; Generations; Growth and Development function; Guanine Nucleotide Exchange Factors; Guanosine Triphosphate; Guanosine Triphosphate Phosphohydrolases; Health; Homeostasis; Individual; Kinesin; Laboratories; Life; Light; Mediating; Membrane; Membrane Protein Traffic; Microtubule Bundle; Microtubules; Molecular; Monomeric GTP-Binding Proteins; Myosin ATPase; Pathway interactions; Phenotype; Positioning Attribute; Process; Proteins; Recruitment Activity; Regulation; Role; Signal Pathway; Sister Chromatid; Site; Structural Protein; System; Techniques; Testing; Time; Ubiquitin-mediated Proteolysis Pathway; anillin; cell cortex; cell growth; daughter cell; genetic approach; genetic regulatory protein; inhibitor/antagonist; innovation; insight; migration; mutant; novel; optogenetics; polarized cell; prevent; progenitor; programs; research study; rho; temporal measurement; tool; trafficking

DESCRIPTION (provided by applicant): Successful cell division requires exquisite spatial and temporal control of the cytoskeleton such that the ingressing cleavage furrow forms between the separating sisters chromatids. Contractile ring assembly occurs in the cell cortex, the cytoplasmic region juxtaposed to the plasma membrane. The mechanism by which the master regulator of this process, the small GTPase RhoA, is activated at the equatorial cell cortex is not well understood. New evidence has been obtained that reveals a previously unidentified inhibitory mechanism. Preliminary results suggest that characterization of this inhibitory mechanism will provide insights into how exchange factors promote RhoA activation. These results and evidence from a variety of systems suggest a hypothesis in which plasma membrane targeting of guanine nucleotide exchange factors is a key step in activating GTPase pathways and that, once active, the primary function that GTPases serve is to recruit effectors to the appropriate membrane environment. This hypothesis will be directly tested in the context of cytokinesis using recently developed optogenetic tools that affords control of protein localization and function in living cells using light. Lastly, experiments will be performed to uncover the molecular function of a novel GYF-domain containing protein that regulates RhoA-dependent cortical contractility.

描述（由申请人提供）：成功的细胞分裂需要对细胞骨架进行精确的空间和时间控制，以便在分离的姐妹染色单体之间形成进入的裂解沟。收缩环组装发生在细胞皮层中，即与质膜并列的细胞质区域。这一过程的主调节器，即小 GTP 酶 RhoA，在赤道细胞皮层被激活的机制尚不清楚。 很好理解。获得的新证据揭示了以前未知的抑制机制。初步结果表明，这种抑制机制的表征将为了解交换因子如何促进 RhoA 激活提供见解。这些结果和来自各种系统的证据提出了一种假设，其中鸟嘌呤核苷酸交换因子的质膜靶向是激活 GTP 酶途径的关键步骤，并且一旦激活，GTP 酶的主要功能是将效应子招募到适当的膜环境。这一假设将在胞质分裂的背景下使用最近开发的光遗传学工具进行直接测试，该工具可以利用光控制活细胞中的蛋白质定位和功能。最后，我们将进行实验来揭示一种新型 GYF 结构域蛋白的分子功能，该蛋白可调节 RhoA 依赖性皮质收缩力。