カンダ ショウイチロウ   KANDA Shoichiro
  神田 祥一郎
   所属   埼玉医科大学  医学部 小児科(小児科、新生児科)
   職種   教授
論文種別 学術雑誌(原著)
言語種別 英語
査読の有無 査読あり
表題 Tyrosine phosphorylation-dependent activation of TRPC6 regulated by PLC-γ1 and nephrin: effect of mutations associated with focal segmental glomerulosclerosis.
掲載誌名 正式名:Molecular biology of the cell
略  称:Mol Biol Cell
ISSNコード:19394586/10591524
掲載区分国外
巻・号・頁 22(11),1824-35頁
著者・共著者 Kanda Shoichiro, Harita Yutaka, Shibagaki Yoshio, Sekine Takashi, Igarashi Takashi, Inoue Takafumi, Hattori Seisuke
発行年月 2011/06
概要 Mutations in the TRPC6 gene are found in patients with focal segmental glomerulosclerosis (FSGS), a proteinuric disease characterized by dysregulated function of renal glomerular epithelial cells (podocytes). We demonstrate here that tyrosine phosphorylation of TRPC6 induces a complex formation with phospholipase C (PLC)-γ1, which is prerequisite for TRPC6 surface expression. Furthermore, nephrin, an adhesion protein between the foot processes of podocytes, binds to phosphorylated TRPC6 via its cytoplasmic domain, competitively inhibiting TRPC6-PLC-γ1 complex formation, TRPC6 surface localization, and TRPC6 activation. Importantly, FSGS-associated mutations render the mutated TRPC6s insensitive to nephrin suppression, thereby promoting their surface expression and channel activation.
DOI 10.1091/mbc.E10-12-0929
PMID 21471003