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Phosphorylation of collapsin response mediator protein 2 on Tyr-479 regulates CXCL12-induced T lymphocyte migration.

Abstract : In the central nervous system, collapsin response mediator protein 2 (CRMP2) is a transducer protein that supports the semaphorin-induced guidance of axons toward their cognate target. However, we previously showed that CRMP2 is also expressed in immune cells and plays a crucial role in T lymphocyte migration. Here we further investigated the molecular mechanisms underlying CRMP2 function in chemokine-directed T-cell motility. Examining Jurkat T-cells treated with the chemokine CXCL12, we found that 1) CXCL12 induces a dynamic re-localization of CRMP2 to uropod, the flexible structure of migrating lymphocyte, and increases its binding to the cytoskeletal protein vimentin; 2) CXCL12 decreases phosphorylation of the glycogen synthase kinase-3beta-targeted residues CRMP2-Thr-509/514; and 3) tyrosine Tyr-479 is a new phosphorylation CRMP2 residue and a target for the Src-family kinase Yes. Moreover, phospho-Tyr-479 increased under CXCL12 signaling while phospho-Thr-509/514 decreased. The functional importance of this tyrosine phosphorylation was demonstrated by Y479F mutation that strongly reduced CXCL12-mediated T-cell polarization and motility as tested in a transmigration model and on neural tissue. We propose that differential phosphorylation by glycogen synthase kinase-3beta and Yes modulates the contribution of CRMP2 to cytoskeletal reorganization during chemokine-directed T-cell migration. In addition to providing a novel mechanism for T lymphocyte motility, our findings reveal CRMP2 as a transducer of chemokine signaling.
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https://www.hal.inserm.fr/inserm-00398974
Contributor : Pascale Giraudon Andrieux <>
Submitted on : Thursday, June 25, 2009 - 1:31:36 PM
Last modification on : Thursday, November 21, 2019 - 2:24:29 AM
Long-term archiving on: : Tuesday, June 15, 2010 - 6:49:01 PM

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Michel Varrin-Doyer, Peggy Vincent, Sylvie Cavagna, Nathalie Auvergnon, Nelly Noraz, et al.. Phosphorylation of collapsin response mediator protein 2 on Tyr-479 regulates CXCL12-induced T lymphocyte migration.. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2009, 284 (19), pp.13265-76. ⟨10.1074/jbc.M807664200⟩. ⟨inserm-00398974⟩

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