Cytoskeleton - Membrane Interactions

细胞骨架-膜相互作用

基本信息

批准号：
7929084
负责人：
ELIZABETH J. LUNA
金额：
$ 9.79万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2010-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7929084
关键词：
Actin-Binding Protein Actinin Actins Adhesions Adhesives Affect Anastomosis - action Behavior Binding Cell Adhesion Cell Line Cell Nucleus Cell physiology Cells Cholesterol Complex Cytoskeletal Modeling Cytoskeleton DNA Sequence Rearrangement Detergents Development Diabetes Mellitus Dominant-Negative Mutation Drug usage Epitopes Exhibits Extracellular Signal Regulated Kinases F-Actin Focal Adhesions Funding GTP-Binding Proteins Goals Immune System Diseases Inhibition of Matrix Metalloproteinases Pathway Integrins Link Lipids Liquid substance Malignant Epithelial Cell Matrix Metalloproteinases Mediating Membrane Membrane Microdomains Membrane Protein Traffic Membrane Proteins Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases Molecular Muscular Dystrophies Myosin ATPase Myosin Type I Myosin Type II Neoplasm Metastasis Phosphotransferases Process Protein Kinase C Protein Tyrosine Kinase Proteins Regulation Resistance Role Signal Pathway Signal Transduction Signaling Protein Smooth Muscle Stimulus Stress Fibers Structure Testing alpha Actinin base cancer cell cdc42 GTP-Binding Protein cell motility density extracellular flotillin fodrin insight matrix metalloproteinase 25 membrane skeleton membrane-type matrix metalloproteinase mutant neoplastic cell neutrophil novel overexpression scaffold src-Family Kinases trafficking tumor

项目摘要

DESCRIPTION (provided by applicant): Both the actin cytoskeleton and cholesterol-rich liquid-ordered membrane domains, also called 'lipid rafts', are involved in signal transduction during cell adhesion, motility, survival, and membrane trafficking. However, the underlying molecular mechanisms are unclear. This application proposes the continued study of a new type of membrane skeleton, first described and characterized in the current funding period, that may represent a 'missing link' in understanding actin and myosin involvement in lipid raft signaling. Detergent-resistant membranes containing this membrane skeleton (DRM-H) exhibit a higher buoyant density than do other cholesterol-rich membrane fractions due to the tight association of lipid raft organizing proteins (flotillins, stomatin) and signaling proteins (Src family kinases, heterotrimeric Gi proteins, matrix metalloproteinase) with filamentous actin, myosins I and II, and other membrane skeleton proteins (alpha-actinin, fodrin, supervillin). DRM-H-related membrane skeletons are present in many motile cells and apparently regulate cell adhesion, contractility, and signaling to extracellularly regulated kinases (ERK1/2). We propose that the DRM-H membrane skeleton is involved in Src and/or ERK signaling by promoting local rearrangements of lipid raft-associated proteins. Supervillin, a membrane-proximal protein that also binds directly to actin and myosin II, appears to be a key control point for this regulation. To test these hypotheses, we propose to: (1) elucidate the roles of actin, myosin, supervillin, and other DRM-H proteins in the formation and reorganization of signaling scaffolds; (2) explore the mechanisms by which DRM-H proteins modulate focal adhesion function and cellular contractility; and (3) determine the role of the DRM-H membrane skeleton during membrane trafficking. These studies describe a novel mechanism for the attachment of actin and myosin II to cholesterol-rich membrane domains and will provide insight into cytoskeletal regulatory mechanisms in these domains. The long-range goal of this project is to understand how actin-based membrane skeletons function during cell motility, adhesion, and signaling. This information will increase our understanding of both normal cellular behaviors and pathological conditions associated with immune dysfunction, cancer cell invasion, muscular dystrophy, diabetes, and developmental abnormalities.

描述（由申请人提供）：肌动蛋白细胞骨架和富含胆固醇的液体液膜结构域，也称为“脂质筏”，参与细胞粘附，运动，生存和膜运输过程中的信号转导。然而，基本的分子机制尚不清楚。该应用程序提出了对新型的膜骨骼的持续研究，该膜骨骼首先描述和表征当前的资金期，这可能代表了理解肌动蛋白和肌球蛋白参与脂质筏信号传导的“缺失链接”。与其他富含胆固醇的膜分数相比，由于脂质RAFT组织蛋白（氟丁氏蛋白，臭舌蛋白）和信号蛋白（SRC家族激酶，丝酶，fillimimimimiment gi蛋白，gi proties gi proties gi ote蛋白，gii蛋白质），含有该膜骨骼（DRM-H）的耐洗涤剂的抗膜比其他富含胆固醇的膜级分表现出更高的浮力密度。肌动蛋白，肌球蛋白I和II以及其他膜骨架蛋白（α-肌动蛋白，禽类蛋白，SuperVillin）。与DRM-H相关的膜骨骼存在于许多运动细胞中，并且显然调节细胞粘附，收缩力和信号传导至细胞外调节激酶（ERK1/2）。我们建议通过促进与脂质筏相关蛋白的局部重排来参与SRC和/或ERK信号传导。 Supervillin是一种直接与肌动蛋白和肌球蛋白II结合的膜蛋白质，似乎是该调节的关键控制点。为了检验这些假设，我们建议：（1）阐明肌动蛋白，肌球蛋白，超级甲基林和其他DRM-H蛋白在信号支架的形成和重组中的作用；（2）探索DRM-H蛋白调节局灶性粘附功能和细胞收缩力的机制；（3）确定在膜运输过程中DRM-H膜骨骼的作用。这些研究描述了肌动蛋白和肌球蛋白II与富含胆固醇的膜结构域的附着的新型机制，并将洞悉这些结构域中细胞骨架调节机制。该项目的远距离目标是了解基于肌动蛋白的膜骨架如何在细胞运动，粘附和信号传导过程中起作用。这些信息将增加我们对与免疫功能障碍，癌细胞侵袭，肌肉营养不良，糖尿病和发育异常相关的正常细胞行为和病理状况的理解。

项目成果

期刊论文数量（58）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Supervillin modulation of focal adhesions involving TRIP6/ZRP-1.

DOI：
10.1083/jcb.200512051
发表时间：
2006-07-31
期刊：
JOURNAL OF CELL BIOLOGY
影响因子：
7.8
作者：
Takizawa, Norio;Smith, Tara C;Nebl, Thomas;Crowley, Jessica L;Palmieri, Stephen J;Lifshitz, Lawrence M;Ehrhardt, Anka G;Hoffman, Laura M;Beckerle, Mary C;Luna, Elizabeth J
通讯作者：
Luna, Elizabeth J

Optimization of nutrition factors on chitinase production from a newly isolated Chitiolyticbacter meiyuanensis SYBC-H1.

DOI：
10.1590/s1517-838220120001000019
发表时间：
2012-01
期刊：
Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology]
影响因子：
0
作者：
Hao Z;Cai Y;Liao X;Zhang X;Fang Z;Zhang D
通讯作者：
Zhang D

A membrane cytoskeleton from Dictyostelium discoideum. II. Integral proteins mediate the binding of plasma membranes to F-actin affinity beads.

来自盘基网柄菌的膜细胞骨架。