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起着核心作用，但我们对它在胚胎发育过程中的调节和维持知之甚少。此外，质膜和细胞骨架之间的联系在细胞周期中是如何动态转化的还不清楚。质膜相关蛋白，发动蛋白在胞质分裂和极性中具有重要但不确定的作用。近年来，研究取得了相当大的进展，证明发动蛋白调节各种膜细胞骨架事件。虽然很明显，发动蛋白可以调节，甚至连接膜的细胞骨架，它仍然是完全不清楚发动蛋白如何协调和维持这些重要的事件在发展过程中。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。这项研究计划的目的是定义和确定的因素，调节细胞质分裂和极性过程中发生的膜细胞骨架事件，并确定如何发动蛋白协调这些过程。该建议的中心假设是，发动蛋白的功能，时间和空间控制胞质分裂机制和影响胚胎极性。在已发表的强有力的初步数据的指导下，我们计划通过追求以下三个目标来测试我们的中心假设并实现本申请的目标：1）表征发动蛋白在动物细胞胞质分裂期间的作用; 2）确定发动蛋白在极性维持期间的贡献; 3）鉴定和表征胚胎发育期间对膜重塑和维持至关重要的细胞周期因子。拟议的工作是创新的，因为它利用了一种新的手段来识别和表征在细胞周期中受到高度调节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动胞质分裂、极性以及膜生物学领域的发展。与公共卫生的相关性：了解质膜在发育过程中是如何调节和维持的是最感兴趣的，因为所确定的因素预计将为预防和治疗干预提供新的目标，这将有助于越来越多的人患有癌症，发育障碍和年龄相关的异常。(End摘要）

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)