Li C, Ruotsalainen V, Tryggvason K, Shaw A S, Miner J H
Renal Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Am J Physiol Renal Physiol. 2000 Oct;279(4):F785-92. doi: 10.1152/ajprenal.2000.279.4.F785.
CD2-associated protein (CD2AP) is an adapter molecule that can bind to the cytoplasmic domain of nephrin, a component of the glomerular slit diaphragm. Mice lacking CD2AP exhibit a congenital nephrotic syndrome characterized by extensive foot process effacement, suggesting that CD2AP-nephrin interactions are critical to maintaining slit diaphragm function. We have examined the patterns of expression of both CD2AP and nephrin in developing mouse and human kidney. Both proteins were first detected in developing podocytes at the capillary loop stage of glomerulogenesis and eventually became concentrated near the glomerular basement membrane. CD2AP was also observed diffusely in collecting duct and apically in many cells of proximal and distal tubule. Kidneys from Cd2ap -/- mice initially exhibited normal nephrin localization, but as the mice aged and foot processes became effaced, nephrin disappeared. In laminin-beta(2) mutant mice exhibiting nephrotic syndrome, CD2AP in glomeruli was aberrantly localized in a primarily punctate pattern. Extensive extrarenal expression of CD2AP was observed in endothelial and epithelial cells, in many cases with a specific subcellular localization. Together, these results suggest that CD2AP is not only involved in maintaining the slit diaphragm but may also have a general role in maintaining specialized subcellular architecture. The severity of kidney disease in Cd2ap mutant mice may have eclipsed manifestation of defects in other tissues.
CD2相关蛋白（CD2AP）是一种衔接分子，可与肾小球裂孔隔膜的组成成分nephrin的胞质结构域结合。缺乏CD2AP的小鼠表现出先天性肾病综合征，其特征为广泛的足突消失，这表明CD2AP与nephrin的相互作用对于维持裂孔隔膜功能至关重要。我们研究了CD2AP和nephrin在发育中的小鼠和人类肾脏中的表达模式。这两种蛋白最初在肾小球发生的毛细血管袢阶段的发育中的足细胞中被检测到，并最终在肾小球基底膜附近聚集。在集合管中也观察到CD2AP呈弥漫性分布，在近端和远端小管的许多细胞中呈顶端分布。Cd2ap -/-小鼠的肾脏最初表现出正常的nephrin定位，但随着小鼠年龄增长和足突消失，nephrin消失。在表现出肾病综合征的层粘连蛋白β(2)突变小鼠中，肾小球中的CD2AP异常定位，主要呈点状分布。在血管内皮细胞和上皮细胞中观察到CD2AP在肾外广泛表达，在许多情况下具有特定的亚细胞定位。总之，这些结果表明CD2AP不仅参与维持裂孔隔膜，还可能在维持特殊的亚细胞结构中发挥一般作用。Cd2ap突变小鼠的肾脏疾病严重程度可能掩盖了其他组织中缺陷的表现。
