α(v)β₅ Integrin recruits the CrkII-Dock180-Rac1 complex for phagocytosis of apoptotic cells

TY - JOUR

T1 - α(v)β5 Integrin recruits the CrkII-Dock180-Rac1 complex for phagocytosis of apoptotic cells

AU - Albert, Matthew L.

AU - Kim, Jong Ii

AU - Birge, Raymond B.

PY - 2000

Y1 - 2000

N2 - 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 α(v)β5 receptor mediates both binding and internalization of apoptotic cells. Internalization is dependent upon signalling through the β5 cytoplasmic tail, and engagement of the α(v)β5 heterodimer results in recruitment of the p13O(cas)-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 celts 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 α(v)β5 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.

AB - 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 α(v)β5 receptor mediates both binding and internalization of apoptotic cells. Internalization is dependent upon signalling through the β5 cytoplasmic tail, and engagement of the α(v)β5 heterodimer results in recruitment of the p13O(cas)-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 celts 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 α(v)β5 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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U2 - https://doi.org/10.1038/35046549

DO - https://doi.org/10.1038/35046549

M3 - Article

C2 - 11146654

SN - 1465-7392

VL - 2

SP - 899

EP - 905

JO - Nature cell biology

JF - Nature cell biology

IS - 12

ER -