Palazzo Alexander F, Eng Christina H, Schlaepfer David D, Marcantonio Eugene E, Gundersen Gregg G
Department of Anatomy and Cell Biology, Columbia University, New York, NY 10032, USA.
Science. 2004 Feb 6;303(5659):836-9. doi: 10.1126/science.1091325.
Microtubule (MT) stabilization is regulated by the small guanosine triphosphate (GTP)-binding protein Rho and its effector, mammalian homolog of Diaphanous (mDia), in migrating cells, but factors responsible for localized stabilization at the leading edge are unknown. We report that integrin-mediated activation of focal adhesion kinase (FAK) at the leading edge is required for MT stabilization by the Rho-mDia signaling pathway in mouse fibroblasts. MT stabilization also involved FAK-regulated localization of a lipid raft marker, ganglioside GM1, to the leading edge. The integrin-FAK signaling pathway may facilitate Rho-mDia signaling through GM1, or through a specialized membrane domain containing GM1, to stabilize MTs in the leading edge of migrating cells.
在迁移细胞中,微管(MT)的稳定由小GTP结合蛋白Rho及其效应蛋白——哺乳动物Diaphanous同源物(mDia)调控,但负责在前缘局部稳定的因子尚不清楚。我们报告,在小鼠成纤维细胞中,Rho-mDia信号通路介导的MT稳定需要整合素介导的粘着斑激酶(FAK)在前缘激活。MT稳定还涉及FAK调节的脂筏标志物神经节苷脂GM1在前缘的定位。整合素-FAK信号通路可能通过GM1或通过含有GM1的特殊膜结构域促进Rho-mDia信号传导,以稳定迁移细胞前缘的MT。