Rap1 potentiates endothelial cell junctions by spatially controlling myosin I activity and actin organization

Koji Ando, Shigetomo Fukuhara, Takahiro Moriya, Yutaro Obara, Norimichi Nakahata, Naoki Mochizuki

研究成果: Article査読

89 被引用数 (Scopus)

抄録

Reorganization of the actin cytoskeleton is responsible for dynamic regulation of endothelial cell (EC) barrier function. Circumferential actin bundles (CAB) promote formation of linear adherens junctions (AJs) and tightening of EC junctions, whereas formation of radial stress fibers (RSF) connected to punctate AJs occurs during junction remodeling. The small GTPase Rap1 induces CAB formation to potentiate EC junctions; however, the mechanism underlying Rap1-induced CAB formation remains unknown. Here, we show that myotonic dystrophy kinase-related CDC42-binding kinase (MRCK)-mediated activation of non-muscle myosin II (NM-II) at cell-cell contacts is essential for Rap1-induced CAB formation. Our data suggest that Rap1 induces FGD5-dependent Cdc42 activation at cell-cell junctions to locally activate the NM-II through MRCK, thereby inducing CAB formation. We further reveal that Rap1 suppresses the NM-II activity stimulated by the Rho-ROCK pathway, leading to dissolution of RSF. These findings imply that Rap1 potentiates EC junctions by spatially controlling NM-II activity through activation of the Cdc42-MRCK pathway and suppression of the Rho-ROCK pathway.

本文言語English
ページ(範囲)901-916
ページ数16
ジャーナルJournal of Cell Biology
202
6
DOI
出版ステータスPublished - 2013
外部発表はい

ASJC Scopus subject areas

  • 細胞生物学

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