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Role of chimaerins, a group of Rac-specific GTPase activating proteins, in T-cell receptor signaling

AuthorsCaloca, María J. ; Delgado, Pilar ; Alarcón, Balbino ; Bustelo, Xosé R.
Issue Date2008
CitationCellular Signalling 20(4): 758-770 (2008)
AbstractChimaerins are GTPase-activating proteins that inactivate the GTP-hydrolase Rac1 in a diacylglycerol-dependent manner. To date, the study of chimaerins has been done mostly in neuronal cells. Here, we show that α2- and β2-chimaerin are expressed at different levels in T-cells and that they participate in T-cell receptor signaling. In agreement with this, we have observed that α2- and β2-chimaerins translocate to the T-cell/B-cell immune synapse and, using both gain- and loss-of-function approaches, demonstrated that their catalytic activity is important for the inhibition of the T-cell receptor- and Vav1-dependent stimulation of the transcriptional factor NF-AT. Mutagenesis-based approaches have revealed the molecular determinants that contribute to the biological program of chimaerins during T-cell responses. Unexpectedly, we have found that the translocation of chimaerins to the T-cell/B-cell immune synapse does not rely on the canonical binding of diacylglycerol to the C1 region of these GTPase-activating proteins. Taken together, these results identify chimaerins as candidates for the downmodulation of Rac1 in T-lymphocytes and, in addition, uncover a novel regulatory mechanism that mediates their activation in T-cells. © 2007 Elsevier Inc. All rights reserved.
Identifiersdoi: 10.1016/j.cellsig.2007.12.015
issn: 0898-6568
Appears in Collections:(IBMCC) Artículos
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