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Molecular Genetics of Hemicentin

半星素的分子遗传学

基本信息

批准号：
7037474
负责人：
BRUCE E VOGEL
金额：
$ 24.36万
依托单位：
UNIVERSITY OF MD BIOTECHNOLOGY INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-04-01 至 2008-03-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Hemicentin is a novel extracellular matrix (ECM) protein first identified in C. elegans by the PI and co-workers. Hemicentin has a simple modular structure: 48 tandem immunoglobulin repeats flanked by unique ends that are highly conserved in two human hemicentin orthologs. ECM proteins provide regulatory and structural information that organizes growing cells into complex 3-dimensional tissues by influencing cell proliferation, differentiation, adhesion and migration. However, our understanding of the mechanisms by which information is transmitted from the ECM and interpreted by cells is not complete. Based on the mutant phenotype and protein localization studies, the PI proposes that the function of hemicentin is to refine broad regions of cell contact into distinct, line-shaped cell junctions and that this function is dependent upon the assembly of hemicentin into fine tracks. Hemicentin is synthesized and secreted by muscle cells but hemicentin tracks assemble at distant sites. This implies that these sites have a mechanism to recruit hemicentin and support its assembly that may involve a cell surface receptor and/or other ECM molecules. To determine the mechanism of hemicentin's influence on tissue organization, the proposed studies will utilize the powerful molecular and transgenic techniques possible with C. elegans to: (1) dissect hemicentin into functional domains that mediate targeting to sites of assembly, assembly into tracks at these sites, and ability to organize cell junctions, (2) identify specific cell surface receptors and/or ECM molecules at secondary sites that recruit hemicentin and support its assembly and (3) biochemically and immunologically characterize the hemicentin protein and assembled hemicentin tracks. The long-term goal is to determine how ECM proteins transmit information to cells, how this information is interpreted by cells to specify the architecture of complex 3-dimensional tissues and how genetic defects in ECM proteins affect this process.

描述（由申请人提供）：半纤维素是一种新型细胞外基质 (ECM)蛋白质首先在C.被PI和同事们发现了半纤维蛋白具有简单的模块化结构：48个串联免疫球蛋白重复序列两侧是两个人类半蛋白中高度保守的独特末端直系同源物。ECM蛋白提供调节和结构信息，将生长中的细胞组织成复杂的三维组织增殖、分化、粘附和迁移。但我们的了解信息通过何种机制从 ECM和细胞解释是不完整的。基于突变表型和蛋白定位研究，PI提出半纤维素的功能是将细胞接触的广泛区域细化为独特的，线形的细胞连接，这种功能依赖于将半纤维素组装成精细的轨道。半纤维素是合成的，由肌肉细胞分泌，但半纤维素轨道在远处聚集。这这意味着这些网站有一种机制，以招募半蛋白和支持其功能。在一些实施方案中，ECM分子可以是可涉及细胞表面受体和/或其它ECM分子的组装体。为了确定半纤维素对组织结构影响的机制，拟议的研究将利用强大的分子和转基因技术，技术可能与C。elegans： (1)将半蛋白分解成介导靶向位点的功能结构域组装，组装成轨道在这些网站，并有能力组织细胞连接，（2）识别特定的细胞表面受体和/或ECM分子募集半蛋白并支持其组装的次级位点和（3）生物化学和免疫学表征半纤维素蛋白，组装的半纤维素痕迹。长期目标是确定ECM蛋白如何将信息传递到单元，单元如何解释此信息以指定体系结构复杂的三维组织，以及ECM蛋白的遗传缺陷如何影响这个过程