pTRAPs: Transmembrane adaptors in innate immune signaling

Transmembrane adaptor proteins (TRAPs) are protein scaffolds and signaling regulators with established roles in signal-induced activation of lymphocytes. A subset of the TRAP family, the palmitoylated TRAPs (pTRAPs), are increasingly emerging with additional roles in innate immune cells. Targeted to lipid rafts, tetraspannin-enriched microdomains, and protein microclusters in membranes, pTRAP scaffolds exert spatiotemporal regulation by recruiting signaling kinases, particularly Src and Syk family members, as well as Csk, and other effectors. In this way, pTRAPs modulate signaling and influence resulting cell responses, including the selective output of inflammatory cytokines and other mediators. Here, we review studies revealing that different pTRAPs work together, often with overlapping or redundant roles, for positive and negative regulation of key innate immune pathways, including Fc receptor and pattern recognition receptor signaling. Recent findings show that pTRAPs can bind directly to innate immune receptors, in addition to other transmembrane binding partners. Thus, pTRAPs are important, multifunctional scaffolds in pathways that are fundamental to diverse innate immune responses.