Research ArticleImmunology

Essential Role of DAP12 Signaling in Macrophage Programming into a Fusion-Competent State

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Science Signaling  28 Oct 2008:
Vol. 1, Issue 43, pp. ra11
DOI: 10.1126/scisignal.1159665

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Setting the Stage for Fusion

DAP12 is an immunotyrosine-based activation motif (ITAM)–containing adaptor protein that interacts with various surface receptors to initiate downstream signaling processes. In the absence of functional DAP12, macrophages fail to fuse to form multinucleated giant cells, an enigmatic immune response involved in granulomatous conditions and the foreign body reaction. In vitro studies showed that DAP12, its associated receptor TREM-2, and the downstream protein tyrosine kinase Syk were all important for maximal fusion capacity of macrophages. In vivo, loss of DAP12 function resulted in the formation of fewer giant cells in response to implantation of a foreign body. Unexpectedly, loss of DAP12 appeared to alter the gene expression profile of the macrophages, rendering them less fusion competent, without compromising their apparent differentiation.

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