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PLoS One. 2014 Aug 18;9(8):e105561. doi: 10.1371/journal.pone.0105561. eCollection 2014.

Mst1 directs Myosin IIa partitioning of low and higher affinity integrins during T cell migration.

Author information

1
Department of Pathology and Immunology, Washington University, St. Louis, Missouri, United States of America.
2
Genomics Institute of the Novartis Research Foundation, San Diego, California, United States of America.
3
Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, United States of America.
4
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America.
5
Department of Pathology and Immunology, Washington University, St. Louis, Missouri, United States of America; Departments of Pathology and Microbiology & Immunology, The Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, United States of America.

Abstract

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.

PMID:
25133611
PMCID:
PMC4136924
DOI:
10.1371/journal.pone.0105561
[Indexed for MEDLINE]
Free PMC Article

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