Research ArticleImmunology

Vav1-Mediated Scaffolding Interactions Stabilize SLP-76 Microclusters and Contribute to Antigen-Dependent T Cell Responses

Sci. Signal.  08 Mar 2011:
Vol. 4, Issue 163, pp. ra14
DOI: 10.1126/scisignal.2001178

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More than the Sum of Its Parts

Vav1 is a guanine nucleotide exchange factor (GEF) that is required for transducing signals from the T cell receptor (TCR). Vav1 synergizes with the adaptor protein SLP-76, which forms microclusters in activated T cells, and disruption of these microclusters inhibits T cell activation. Sylvain et al. performed live-cell imaging and functional analysis of antigen-stimulated cells expressing various mutant Vav1 proteins. The C terminus of Vav1 contains Src homology domains, and the N terminus contains a calponin homology domain and the GEF domain. The C terminus of Vav1 was required for the recruitment of Vav1 into SLP-76 microclusters but was not sufficient to stabilize the microclusters. Although the GEF activity of Vav1 was required for TCR signaling, stabilization of the microclusters was not affected by activation or inactivation of the GEF activity Vav1; this finding suggests that Vav1 enhances TCR signaling through its GEF activity and by increasing the persistence of SLP-76 microclusters through multiple scaffolding interactions.