Mst1 Directs Myosin IIa Partitioning of Low and Higher Affinity Integrins during T Cell Migration

作者：Xu Xiaolu; Jaeger Emily R; Wang Xinxin; Lagler Ferrez Erica; Batalov Serge; Mathis Nancy L; Wiltshire Tim; Walker John R; Cooke Michael P; Sauer Karsten^*; Huang Yina H

来源：PLos One, 2014, 9(8): e105561.

DOI：10.1371/journal.pone.0105561

Chemokines promote T cell migration by transmitting signals that induce T cell polarization and integrin activation and adhesion. Mst1 kinase is a key signal mediator required for both of these processes; however, its molecular mechanism remains unclear. Here, we present a mouse model in which Mst1 function is disrupted by a hypomorphic mutation. Microscopic analysis of Mst1-deficient CD4 T cells revealed a necessary role for Mst1 in controlling the localization and activity of Myosin IIa, a molecular motor that moves along actin filaments. Using affinity specific LFA-1 antibodies, we identified a requirement for Myosin IIa-dependent contraction in the precise spatial distribution of low and higher affinity LFA-1 on the membrane of migrating T cells. Mst1 deficiency or Myosin inhibition resulted in multipolar cells, difficulties in uropod detachment and mis-localization of low affinity LFA-1. Thus, Mst1 regulates Myosin IIa dynamics to organize high and low affinity LFA-1 to the anterior and posterior membrane during T cell migration.

• 出版日期2014-8-18