Spatiotemporal regulation of the kinase Mst1 by binding protein RAPL is critical for lymphocyte polarity and adhesion.
RAPL, a protein that binds the small GTPase Rap1, is required for efficient immune cell trafficking. Here we have identified the kinase Mst1 as a critical effector of RAPL. RAPL regulated the localization and kinase activity of Mst1. 'Knockdown' of the gene encoding Mst1 demonstrated its requirement for the induction of both a polarized morphology and integrin LFA-1 clustering and adhesion triggered by chemokines and T cell receptor ligation. RAPL and Mst1 localized to vesicular compartments and dynamically translocated with LFA-1 to the leading edge upon Rap1 activation, suggesting a regulatory function for the RAPL-Mst1 complex in intracellular transport of LFA-1. Our study demonstrates a previously unknown function for Mst1 of relaying the Rap1-RAPL signal to induce cell polarity and adhesion of lymphocytes.
Katagiri
Koko
K
Department of Molecular Genetics, Institute of Biomedical Science, Kansai Medical University, Osaka 570-8506, Japan.
Imamura
Masashi
M
Kinashi
Tatsuo
T
D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D016764:Cell Polarity / Q000235:genetics; D017228:Hepatocyte Growth Factor / Q000819:agonists / Q000032:analysis / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008214:Lymphocytes / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000819:agonists / Q000032:analysis / Q000378:metabolism*; D022161:Transport Vesicles / Q000737:chemistry / Q000378:metabolism; D015854:Up-Regulation; D020827:rap1 GTP-Binding Proteins / Q000819:agonists / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins
D017228:Hepatocyte Growth Factor; D016169:Lymphocyte Function-Associated Antigen-1; D011518:Proto-Oncogene Proteins; D020827:rap1 GTP-Binding Proteins; C082332:macrophage stimulating protein; C455831:Rassf5 protein, mouse; D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins