Cellular and molecular biology of plakin crosslinking proteins in myogenic cells

肌原细胞中斑块交联蛋白的细胞和分子生物学

• 批准号: 261511-2008
• 负责人: BoudreauLarivière, Céline
• 金额: $ 1.6万
• 依托单位: Laurentian University of Sudbury
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2009
• 资助国家: 加拿大
• 起止时间: 2009-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=426642
• 关键词: Cellular; molecular; biology; plakin; crosslinking

Multicellular organisms are comprised of a variety of cell types with unique shapes that are dictated primarily by scaffolding molecules located inside the cells. The ability of cells to either maintain or change their conformation has profound and direct implications on their function within an organism. Understanding how scaffolding proteins influence cell shape and function is the primary objective of the present grant application. The proposed studies are particularly focused on understanding the functions of one family of scaffolding proteins known as plakins. Plakins are particularly enriched in tissues that undergo significant mechanical stress such as skin and muscle and are thought to preserve the organization of these tissues when they are stretched or compressed. In humans, genetic lesions associated with certain plakin family members result in skin blistering disorders and muscular dystrophies. The applicant is particularly interested in determining the importance of plakins in skeletal muscle. To achieve this objective, studies to assess the localization of bullous pemphigoid antigen 1 (Bpag1), one specific plakin family member, in muscle tissue and studies to identify Bpag1-interacting proteins are envisioned. Furthermore, studies to determine the relative contributions of different plakin family members during the proliferation and differentiation of muscle cells are proposed. Collectively, these studies are expected to provide new insights into the fundamental structure and function of muscle fibers and will enhance our understanding of myopathies that are related to disruptions of the muscle fiber architecture.

多细胞生物体由多种具有独特形状的细胞类型组成，这些细胞主要由位于细胞内的支架分子决定。细胞维持或改变自身构象的能力对它们在生物体内的功能有着深远而直接的影响。了解支架蛋白如何影响细胞的形状和功能是目前拨款申请的主要目标。拟议中的研究特别侧重于了解一种名为Plakins的支架蛋白家族的功能。白蛋白尤其富含承受巨大机械应力的组织，如皮肤和肌肉，当这些组织被拉伸或压缩时，被认为可以保存这些组织的组织。在人类中，与某些Plakin家族成员相关的遗传损害会导致皮肤起泡疾病和肌肉营养不良。申请人对确定Plakins在骨骼肌中的重要性特别感兴趣。为了实现这一目标，大疱性类天疱疮抗原1(Bpag1)是一种特殊的Plakin家族成员，它在肌肉组织中的定位以及鉴定Bpag1相互作用蛋白的研究正在进行中。此外，还提出了确定不同plakin家族成员在肌肉细胞增殖和分化过程中的相对贡献的研究。总而言之，这些研究有望为肌肉纤维的基本结构和功能提供新的见解，并将加强我们对与肌肉纤维结构破坏相关的肌病的理解。