Mst1 kinase regulates the actin-bundling protein L-plastin to promote T cell migration

Xiaolu Xu, Xinxin Wang, Elizabeth M. Todd, Emily R. Jaeger, Jennifer L. Vella, Olivia L. Mooren, Yunfeng Feng, Jiancheng Hu, John A. Cooper, Sharon Celeste Morley, Yina H. Huang

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17 Scopus citations

Abstract

Exploring the mechanisms controlling lymphocyte trafficking is essential for understanding the function of the immune system and the pathophysiology of immunodeficiencies. The mammalian Ste20-like kinase 1 (Mst1) has been identified as a critical signaling mediator of T cell migration, and loss of Mst1 results in immunodeficiency disease. Although Mst1 is known to support T cell migration through induction of cell polarization and lamellipodial formation, the downstream effectors of Mst1 are incompletely defined. Mice deficient for the actin-bundling protein L-plastin (LPL) have phenotypes similar to mice lacking Mst1, including decreased T cell polarization, lamellipodial formation, and cell migration.We therefore asked whether LPL functions downstream of Mst1. The regulatory N-terminal domain of LPL contains a consensus Mst1 phosphorylation site at Thr89. We found that Mst1 can phosphorylate LPL in vitro and that Mst1 can interact with LPL in cells. Removal of the Mst1 phosphorylation site by mutating Thr89 to Ala impaired localization of LPL to the actin-rich lamellipodia of T cells. Expression of the T89A LPL mutant failed to restore migration of LPL-deficient T cells in vitro. Furthermore, expression of T89A LPL in LPL-deficient hematopoietic cells, using bone marrow chimeras, failed to rescue the phenotype of decreased thymic egress. These results identify LPL as a key effector of Mst1 and establish a novel mechanism linking a signaling intermediate to an actin-binding protein critical to T cell migration.

Original languageEnglish
Pages (from-to)1683-1691
Number of pages9
JournalJournal of Immunology
Volume197
Issue number5
DOIs
StatePublished - Sep 1 2016

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    Xu, X., Wang, X., Todd, E. M., Jaeger, E. R., Vella, J. L., Mooren, O. L., Feng, Y., Hu, J., Cooper, J. A., Morley, S. C., & Huang, Y. H. (2016). Mst1 kinase regulates the actin-bundling protein L-plastin to promote T cell migration. Journal of Immunology, 197(5), 1683-1691. https://doi.org/10.4049/jimmunol.1600874