Investigating plasma membrane regulation during embryonic development

描述(由申请人提供)： 质膜在细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如何调节和维持知之甚少。此外，细胞膜和底层细胞骨架之间的联系在细胞周期中如何动态变化尚不清楚。质膜相关蛋白Dynamin在细胞质分裂和极性中扮演着重要但尚未确定的角色。近年来，已经取得了相当大的进展，证明了Dynamin调节各种膜-细胞骨架事件。虽然很明显，Dynamin可以调节膜，甚至将膜与细胞骨架联系在一起，但在发育过程中，Dynamin如何协调和维持这些关键事件仍然是完全不清楚的。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。这个研究项目的目的是定义和确定在细胞质分裂和极性过程中调节膜-细胞骨架事件的因素，并确定Dynamin如何协调这些过程。该提议的中心假设是，动力蛋白在时间和空间上控制细胞质分裂机制，并影响胚胎的极性。在已发表和强大的初步数据的指导下，我们计划检验我们的中心假设，并通过追求以下三个目标来实现这一应用的目标：1)表征Dynamin在动物细胞胞质分裂中的作用；2)确定Dynamin在极性维持中的作用；以及3)识别和表征在胚胎发育过程中对膜重构和维持至关重要的细胞周期因子。这项拟议的工作具有创新性，因为它利用了一种新的方法来识别和表征在细胞周期中高度调控的不同质膜结构域的功能。这项拟议的研究意义重大，因为预计其结果将从根本上促进细胞质分裂、极性和膜生物学领域的发展。与公共卫生相关：了解质膜在发育过程中是如何调节和维持的是最重要的，因为已确定的因素有望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、发育障碍和与年龄相关的异常。(摘要结束)

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)