Investigating plasma membrane regulation during embryonic development

研究胚胎发育过程中的质膜调节

基本信息

批准号：
7474136
负责人：
Ahna Renee Skop
金额：
$ 12.78万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-05-15 至 2013-04-30
项目状态：
已结题

项目摘要

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)

描述（由申请人提供）：质膜在细胞因子和极性中起着核心作用，但我们对在胚胎发育过程中如何调节和维持它几乎不了解。此外，在细胞周期中，质膜与潜在细胞骨架之间的关联如何在细胞周期中动态转化。质膜相关的蛋白质在细胞因子和极性中具有必不可少但不确定的作用。近年来，已经取得了相当大的进步，表明动力蛋白调节各种膜骨骼事件。虽然很明显Dynamin可能调节甚至将膜与细胞骨架联系起来，但仍不清楚Dynamin在开发过程中如何坐标并维护这些基本事件。长期目标是更好地了解胚胎发育过程中如何调节和维护质膜。该研究计划的目的是定义和确定调节细胞因子和极性期间发生的膜 - 骨骼事件的因素，并确定动力蛋白如何协调这些过程。该提案的中心假设是，动力蛋白在时间和空间控制细胞因子机械上的功能并影响胚胎极性。在发布且强大的初步数据的指导下，我们计划通过追求以下三个目的来检验我们的中心假设，并实现该应用的目标：1）表征动物细胞中动力蛋白在动物细胞中的作用； 2）确定在极性维持过程中动力蛋白的贡献； 3）识别和表征细胞周期因素对于胚胎发育过程中膜重塑和维护至关重要的细胞周期因子。拟议的工作具有创新性，因为它利用了一种新的手段来识别和表征在细胞周期中高度调节不同质膜结构域的功能。拟议的研究很重要，因为预计结果将从根本上推进细胞因子，极性和膜生物学的领域。与公共卫生的相关性：了解在开发过程中如何调节和维护质膜是最大的兴趣，因为预计确定的因素将为预防和治疗性干预措施提供新的目标，以帮助越来越多的患有癌症，发育障碍，与年龄相关的异常。（抽象的结尾）