Mst1 directs Myosin IIa partitioning of low and higher affinity integrins during T cell migration.
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...
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doaj-a5c321874ad94940ab38b3e079964f672020-11-24T22:08:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0198e10556110.1371/journal.pone.0105561Mst1 directs Myosin IIa partitioning of low and higher affinity integrins during T cell migration.Xiaolu XuEmily R JaegerXinxin WangErica Lagler-FerrezSerge BatalovNancy L MathisTim WiltshireJohn R WalkerMichael P CookeKarsten SauerYina H HuangChemokines 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.http://europepmc.org/articles/PMC4136924?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiaolu Xu Emily R Jaeger Xinxin Wang Erica Lagler-Ferrez Serge Batalov Nancy L Mathis Tim Wiltshire John R Walker Michael P Cooke Karsten Sauer Yina H Huang |
spellingShingle |
Xiaolu Xu Emily R Jaeger Xinxin Wang Erica Lagler-Ferrez Serge Batalov Nancy L Mathis Tim Wiltshire John R Walker Michael P Cooke Karsten Sauer Yina H Huang Mst1 directs Myosin IIa partitioning of low and higher affinity integrins during T cell migration. PLoS ONE |
author_facet |
Xiaolu Xu Emily R Jaeger Xinxin Wang Erica Lagler-Ferrez Serge Batalov Nancy L Mathis Tim Wiltshire John R Walker Michael P Cooke Karsten Sauer Yina H Huang |
author_sort |
Xiaolu Xu |
title |
Mst1 directs Myosin IIa partitioning of low and higher affinity integrins during T cell migration. |
title_short |
Mst1 directs Myosin IIa partitioning of low and higher affinity integrins during T cell migration. |
title_full |
Mst1 directs Myosin IIa partitioning of low and higher affinity integrins during T cell migration. |
title_fullStr |
Mst1 directs Myosin IIa partitioning of low and higher affinity integrins during T cell migration. |
title_full_unstemmed |
Mst1 directs Myosin IIa partitioning of low and higher affinity integrins during T cell migration. |
title_sort |
mst1 directs myosin iia partitioning of low and higher affinity integrins during t cell migration. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC4136924?pdf=render |
work_keys_str_mv |
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