期刊
FASEB JOURNAL
卷 32, 期 3, 页码 1665-1676出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.201700703R
关键词
actin cytoskeleton; signaling; tyrosine kinase; neurotrophin-3
资金
- Deutsche Nierenstiftung
- Zentrum fur Klinische Forschung [Geo2/003/16]
- Deutsche Forschungsgemeinschaft [GE 2158/3-1, SCHW 407/17]
- Cells-in-Motion Cluster of Excellence (University of Munster) [EXC 1003-CiM]
Podocyte malfunction is central to glomerular diseases and is marked by defective podocyte intercellular junctions and actin cytoskeletal dynamics. Podocytes share many morphologic features with neurons, so that similar sets of proteins appear to regulate cell process formation. One such protein is the tropomyosin-related kinase C (TrkC). TrkC deficiency inmice leads to proteinuria as a surrogate of defective kidney filter function. Activation of endogenous TrkC by its ligand neurotrophin-3 resulted in increased podocyte migration-a surrogate of podocyte actin dynamics in vivo. Employing a mutagenesis approach, we found that the Src homologous and collagen-like (Shc) binding site Tyr(516) within the TrkC cytoplasmic domain was necessary for TrkC-induced migration of podocytes. TrkC activation led to a mobility shift of Wiskott-Aldrich syndrome family verprolin-homologous protein (WAVE)-2which is knownto orchestrate Arp2/3 activation and actin polymerization. Chemical inactivation of Erk ormutagenesis of 2 of 4 knownErk target siteswithinWAVE2, Thr(346) and Ser(351), abolishedthe TrkC-induced WAVE2 mobility shift. Knockdown of WAVE2 by shRNA abolished TrkC-induced podocyte migration. In summary, TrkC signals to the podocyte actin cytoskeleton to induce migration by phosphorylating WAVE2 Erk dependently. This signaling mechanism may be important for TrkC-mediated cytoskeletal dynamics in podocyte disease.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据