ADAP is an upstream regulator that precedes SLP-76 at sites of TCR engagement and stabilizes signaling microclusters.

Autor:	Lewis JB; Program in Immunology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA., Scangarello FA; Program in Immunology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA.; Medical Scientist Training Program, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA., Murphy JM; Department of Immunology, Tufts University School of Medicine, Boston, MA 02111, USA., Eidell KP; Program in Immunology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA., Sodipo MO; Department of Immunology, Tufts University School of Medicine, Boston, MA 02111, USA., Ophir MJ; Program in Immunology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA., Sargeant R; Pacific Immunology Corporation, Ramona, CA 92065, USA., Seminario MC; Department of Immunology, Tufts University School of Medicine, Boston, MA 02111, USA., Bunnell SC; Program in Immunology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA stephen.bunnell@tufts.edu.; Department of Immunology, Tufts University School of Medicine, Boston, MA 02111, USA.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2018 Nov 08; Vol. 131 (21). Date of Electronic Publication: 2018 Nov 08.
DOI:	10.1242/jcs.215517
Abstrakt:	Antigen recognition by the T cell receptor (TCR) directs the assembly of essential signaling complexes known as SLP-76 (also known as LCP2) microclusters. Here, we show that the interaction of the adhesion and degranulation-promoting adaptor protein (ADAP; also known as FYB1) with SLP-76 enables the formation of persistent microclusters and the stabilization of T cell contacts, promotes integrin-independent adhesion and enables the upregulation of CD69. By analyzing point mutants and using a novel phospho-specific antibody, we show that Y595 is essential for normal ADAP function, that virtually all tyrosine phosphorylation of ADAP is restricted to a Y595-phosphorylated (pY595) pool, and that multivalent interactions between the SLP-76 SH2 domain and its binding sites in ADAP are required to sustain ADAP phosphorylation. Although pY595 ADAP enters SLP-76 microclusters, non-phosphorylated ADAP is enriched in protrusive actin-rich structures. The pre-positioning of ADAP at the contact sites generated by these structures favors the retention of nascent SLP-76 oligomers and their assembly into persistent microclusters. Although ADAP is frequently depicted as an effector of SLP-76, our findings reveal that ADAP acts upstream of SLP-76 to convert labile, Ca 2+ -competent microclusters into stable adhesive junctions with enhanced signaling potential. Competing Interests: Competing interestsThe authors declare no competing or financial interests. (© 2018. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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