Investigating plasma membrane regulation during embryonic development

描述（由申请人提供）： 质膜在胞质分裂和极性中发挥着核心作用，但我们对它在胚胎发育过程中如何调节和维持知之甚少。此外，质膜和底层细胞骨架之间的关联如何在细胞周期中动态转变尚不清楚。质膜相关蛋白动力蛋白在胞质分裂和极性中具有重要但尚未明确的作用。近年来，已经取得了相当大的进展，证明动力蛋白调节多种膜细胞骨架事件。虽然很明显动力蛋白可以调节甚至连接膜与细胞骨架，但仍然完全不清楚动力蛋白在发育过程中如何协调和维持这些重要事件。长期目标是更好地了解质膜在胚胎发育过程中是如何调节和维持的。该研究计划的目的是定义和识别调节胞质分裂和极性期间发生的膜细胞骨架事件的因素，并确定动力如何协调这些过程。该提案的中心假设是动力蛋白的功能是在时间和空间上控制胞质分裂机制并影响胚胎极性。在已发表的强有力的初步数据的指导下，我们计划测试我们的中心假设，并通过追求以下三个目标来实现本申请的目标：1）表征动力在动物细胞胞质分裂过程中的作用； 2) 确定极性维持过程中动力的贡献； 3) 识别和表征对胚胎发育过程中膜重塑和维持至关重要的细胞周期因子。这项工作具有创新性，因为它利用了一种新方法来识别和表征在细胞周期中受到高度调控的不同质膜结构域的功能。这项研究意义重大，因为预计其结果将从根本上推进胞质分裂、极性以及膜生物学领域的发展。与公共健康的相关性：了解质膜在发育过程中如何调节和维持是最令人感兴趣的，因为所确定的因素预计将为预防和治疗干预措施提供新的目标，从而帮助越来越多的患有癌症、发育障碍和年龄相关异常的人。 （摘要完）

DESCRIPTION (provided by applicant): The plasma membrane plays a central role in cytokinesis and polarity, yet we know very little about how it is regulated and maintained during embryonic development. In addition, how the association between the plasma membrane and underlying cytoskeleton is dynamically transformed during the cell cycle is unclear. The plasma membrane-associated protein, dynamin has an essential yet undefined role in cytokinesis and polarity. In recent years, considerable progress has been made demonstrating that dynamin regulates a variety of membrane-cytoskeletal events. While it is evident that dynamin may regulate and even link membrane to the cytoskeleton, it is still entirely unclear how dynamin coordinates and maintains these essential events during development. The long-term goal is to better understand how the plasma membrane is regulated and maintained during embryonic development. The objective of this research program is to define and identify factors that regulate membrane-cytoskeletal events that occur during cytokinesis and polarity and to determine how dynamin coordinate these processes. The central hypothesis of the proposal is that dynamin functions to temporally and spatially control cytokinesis machinery and influence embryonic polarity. Guided by published and strong preliminary data, we plan to test our central hypothesis and accomplish the objective of this application by pursuing the following three aims: 1) Characterize the role of dynamin during cytokinesis in animal cells; and 2) Determine the contribution of dynamin during polarity maintenance; and 3) Identify and characterize cell-cycle factors critical for membrane remodeling and maintenance during embryonic development. The proposed work is innovative, because it capitalizes on a new means of identifying and characterizing the function of distinct plasma membrane domains that are highly regulated during the cell cycle. The proposed research is significant, because it is expected that the results will fundamentally advance the fields of cytokinesis, polarity as well as membrane biology. Relevance to Public Health: Understanding how the plasma membrane is regulated and maintained during development is of utmost interest because the identified factors are anticipated to provide new targets for preventive and therapeutic interventions that will aid in the growing numbers of persons who have cancer, developmental disorders and age-related abnormalities. (End of Abstract)