αvβ5 integrin recruits the CrkII–Dock180–Rac1 complex for phagocytosis of apoptotic cells

Integrin receptors are important for the phagocytosis of apoptotic cells. However, little is known about their function in mediating internalization, as previous studies used blocking antibodies for the inhibition of binding. Here we show that the αvβ5 receptor mediates both binding and internalization of apoptotic cells. Internalization is dependent upon signalling through the β5 cytoplasmic tail, and engagement of the αvβ5 heterodimer results in recruitment of the p130cas–CrkII–Dock180 molecular complex, which in turn triggers Rac1 activation and phagosome formation. In addition to defining integrin-receptor signalling as critical for the internalization of apoptotic material, our results also constitute the first evidence in human cells that the CED-2–CED-5–CED-10 complex defined in Caenorhabditis elegans is functionally analagous to the CrkII–Dock180–Rac1 molecular complex in mammalian cells. By linking the αvβ5 receptor to this molecular switch, we reveal an evolutionarily conserved signalling pathway that is responsible for the recognition and internalization of apoptotic cells by both professional and non-professional phagocytes.

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