Patrakka Jaakko, Tryggvason Karl
Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, 171 77 Stockholm, Sweden.
Trends Mol Med. 2007 Sep;13(9):396-403. doi: 10.1016/j.molmed.2007.06.006. Epub 2007 Sep 4.
Since the discovery of nephrin, the first integral component of the slit diaphragm to be identified, the podocyte slit pore has become a major focus in research concerning the glomerular filtration barrier. Nephrin is a central component of the glomerular ultrafilter, with both structural and signaling functions. The extracellular domain of nephrin and other components of the slit diaphragm seem to form a porous molecular sieve. The intracellular domain of nephrin is associated with linker proteins, such as CD2-associated protein and Nck proteins that can connect nephrin to the actin cytoskeleton. Alterations in nephrin interactions with other proteins during development or injury can lead to complex signaling reactions aimed at establishing or restoring the filter function.
自从发现nephrin(首个被鉴定出的裂孔隔膜整合成分)以来,足细胞裂孔已成为肾小球滤过屏障研究的主要焦点。Nephrin是肾小球超滤器的核心成分,兼具结构和信号传导功能。Nephrin的细胞外结构域与裂孔隔膜的其他成分似乎形成了一个多孔分子筛。Nephrin的细胞内结构域与连接蛋白相关,如可将nephrin连接至肌动蛋白细胞骨架的CD2相关蛋白和Nck蛋白。在发育过程或损伤期间,nephrin与其他蛋白质相互作用的改变可导致旨在建立或恢复滤过功能的复杂信号反应。