CBAP Functions as a Novel Component in Chemokine-Induced ZAP70-Mediated T-Cell Adhesion and Migration

作者：Yun-Jung Chiang, Kun-Chin Ho, Chien-Tsang Sun, Jeng‐Jiann Chiu, Fang-Jen Scott Lee, Fang Liao, Hsin‐Fang Yang‐Yen, Jeffrey Jong-Young Yen · 发表于：PLoS ONE · 年份：2013 · DOI：10.1371/journal.pone.0061761 · 被引用次数：8 · 研究领域：Cell Adhesion Molecules Research、T-cell and B-cell Immunology、Chemokine receptors and signaling

Activated chemokine receptor initiates inside-out signaling to transiently trigger activation of integrins, a process involving multiple components that have not been fully characterized. Here we report that GM-CSF/IL-3/IL-5 receptor common beta-chain-associated protein (CBAP) is required to optimize this inside-out signaling and activation of integrins. First, knockdown of CBAP expression in human Jurkat T cells caused attenuated CXC chemokine ligand-12 (CXCL12)-induced cell migration and integrin α4β1- and αLβ2-mediated cell adhesion in vitro, which could be rescued sufficiently upon expression of murine CBAP proteins. Freshly isolated CBAP-deficient primary T cells also exhibited diminution of chemotaxis toward CC chemokine ligand-21 (CCL21) and CXCL12, and these chemokines-induced T-cell adhesions in vitro. Adoptive transfer of isolated naive T cells demonstrated that CBAP deficiency significantly reduced lymph node homing ability in vivo. Finally, migration of T cell-receptor-activated T cells induced by inflammatory chemokines was also attenuated in CBAP-deficient cells. Further analyses revealed that CBAP constitutively associated with both integrin β1 and ZAP70 and that CBAP is required for chemokine-induced initial binding of the talin-Vav1 complex to integrin β1 and to facilitate subsequent ZAP70-mediated dissociation of the talin-Vav1 complex and Vav1 phosphorylation. Within such an integrin signaling complex, CBAP likely functions as an adaptor and ultimately lead...