糸球体上皮細胞シグナル伝達系のプロテオミクス解析による蛋白尿発症機序の解明

足细胞之间的特殊细胞间连接被称为裂隙隔膜(SD)，形成了肾脏中肾小球滤过的基本结构框架。此外，越来越多的证据表明，SD在生理和病理状态下也发挥着重要的信号平台作用。神经蛋白是SD的主要成分，在发育中或受损的足细胞中，它是由一种Src家族酪氨酸激酶Fyn磷酸化的。在这项研究中，我们通过蛋白质组学分析寻找与磷酸化的Nephin结合的蛋白质，发现了几种新的相互作用的蛋白质，包括磷脂酶C-γ1PLC-γ1。此外，通过招募和激活PLC-γ1直接参与了钙稳态。这些结果有力地表明SD结构通过PLC-γ1直接与Ca^&lt；2+&gt；信号联系在一起，并证明了SD作为一种多功能信号通路的协调者的新作用。

A specialized intercellular junction between podocytes, known as the slit diaphragm (SD), forms the essential structural framework for glomerular filtration in the kidney. In addition, mounting evidence demonstrates that SD also plays a crucial role as a signaling platform in physiological and pathological states. Nephrin, the major component of SD, is tyrosine phosphorylated by a Src-family tyrosine kinase, Fyn, in developing or injured podocytes. In this study, we performed proteomic analysis searching for proteins binding with phosphorylated Nephrin, and identified several novel interacting protein including phospholipase C-γ1PLC-γ1. Furthermore, phosphorylation of Nephrin is directly involved in Ca^<2+> homeostasis via the recruitment and activation of PLC-γ1. These results strongly suggest that the SD structure is directly linked to Ca^<2+> signaling by PLC-γ1, and demonstrate a novel role of SD as an orchestrator of versatile signaling pathway.