Cytoskeletal/junction relationships during epithelial remodeling events

上皮重塑事件期间的细胞骨架/连接关系

• 批准号: 155397-2013
• 负责人: Vogl, Wayne
• 金额: $ 2.62万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=569454
• 关键词: Cytoskeletal; junction; relationships; during; epithelial

The cell surface is the interface between cells and their environment. Interactions at this interface enable cells to generate movement, to assume specific shapes, to carry out specific functions, and to form multicellular structures. It is not surprising that major elements of the cytoskeleton within animal cells are related to the cell surface, particularly to regions of the surface involved in forming connections both with neighboring cells and with supporting substrates. The long-term objective of my research program is to explore the interaction between intercellular junctions and the cytoskeleton in cells within the context of tissues, and determine how the two systems function together to generate complex remodeling events in cell layers (epithelia) that line the many tubes and cavities in animals. We are particularly interested in how the cytoskeleton and junctions interact to allow cells to detach from their neighbors and to move through epithelia from one compartment of the body to another. Over the next five years we will explore the mechanism by which the cytoskeleton and junctions function to move developing sperm cells through the seminiferous epithelium of the mammalian testis, and to release fully formed sperm cells from this epithelium. We will focus on cytoskeleton-related tubular structures that we propose are sub-cellular machines that internalize and degrade intact intercellular junctions during the extensive epithelial remodeling events that occur during the production of sperm cells. We will characterize these structures at the molecular level and determine if their function is required for the successful movement of the next generation of developing sperm cells further into the epithelium. Our results have already generated a paradigm shift in how biologists view junction disassembly related to sperm release. Over the next few years we anticipate that our results will generate a similar shift in how biologists view the movement of the next generation of developing sperm cells from one compartment to another in the seminiferous epithelium.

细胞表面是细胞与环境之间的界面。在这个界面上的相互作用使细胞能够产生运动，呈现特定的形状，执行特定的功能，并形成多细胞结构。动物细胞内细胞骨架的主要成分与细胞表面有关，特别是与与相邻细胞和支持基质形成连接的表面区域有关，这并不奇怪。我的研究计划的长期目标是探索组织背景下细胞间连接和细胞骨架之间的相互作用，并确定这两个系统如何共同发挥作用，以产生复杂的重塑事件在细胞层（上皮细胞），内衬许多管和腔在动物。我们特别感兴趣的是细胞骨架和连接如何相互作用，使细胞从它们的邻居分离，并通过上皮细胞从身体的一个区室移动到另一个区室。在接下来的五年里，我们将探索细胞骨架和连接的机制，通过该机制，细胞骨架和连接的功能，使发育中的精子细胞穿过哺乳动物睾丸的生精上皮，并从该上皮释放完全形成的精子细胞。我们将专注于细胞凋亡相关的管状结构，我们建议是亚细胞机器，内化和降解完整的细胞间连接在广泛的上皮重塑事件发生在精子细胞的生产过程中。我们将在分子水平上表征这些结构，并确定它们的功能是否是下一代发育中的精子细胞成功进入上皮细胞所必需的。我们的研究结果已经在生物学家如何看待与精子释放相关的连接解体方面产生了范式转变。在接下来的几年里，我们预计我们的研究结果将在生物学家如何看待下一代发育中的精子细胞从生精上皮中的一个隔室到另一个隔室的运动方面产生类似的转变。