Multimolecular Signaling Complexes Enable Syk-mediated Signaling of CD36 Internalization

Overview

Journal Dev Cell

Publisher Cell Press

Specialties Cell Biology
Reproductive Medicine

Date 2013 Feb 12

PMID 23395392

Citations 60

Authors

Bryan Heit

Hani Kim

Gabriela Cosio

Diana Castano

Richard Collins

Clifford A Lowell

Kevin C Kain

William S Trimble

Sergio Grinstein

Affiliations

Soon will be listed here.

Abstract

CD36 is a versatile receptor known to play a central role in the development of atherosclerosis, the pathogenesis of malaria, and the removal of apoptotic cells. Remarkably, the short cytosolically exposed regions of CD36 lack identifiable motifs, which has hampered elucidation of its mode of signaling. Using a combination of phosphoprotein isolation, mass spectrometry, superresolution imaging, and gene silencing, we have determined that the receptor induces ligand internalization through a heteromeric complex consisting of CD36, β1 and/or β2 integrins, and the tetraspanins CD9 and/or CD81. This receptor complex serves to link CD36 to the adaptor FcRγ, which bears an immunoreceptor tyrosine activation motif. By coupling to FcRγ, CD36 is able to engage Src-family kinases and Syk, which in turn drives the internalization of CD36 and its bound ligands.

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