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

Nature Cell Biology volume 2, pages 899–905 (2000)Cite this article

Abstract

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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Figure 1: 293T cells efficiently capture apoptotic cells.
Figure 2: 293T cells capture apoptotic cells in a manner that is similar to immature dendritic cells.
Figure 3: The β5 integrin regulates phagocytosis of apoptotic cells.
Figure 4: αvβ5 activation results in recruitment of the p130cas–CrkII–Dock180 complex.
Figure 5: CrkII is recruited to the membrane for phagosome formation and is critical for the phagocytosis of apoptotic cells.
Figure 6: A role for Rac1 in αvβ5-mediated phagocytosis.

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Acknowledgements

We thank A. Rodriguez for assistance with the IF studies, S. Amigorena, N. Bhardwaj, R. B. Darnell, E. Fajardo and N. Hacohen for helpful discussions and critical comments, D. Cheresh for the αv and β5 gene constructs, R. M. Steinman and M. Nussenzweig for use of the FACScan, T. de Lange for use of the microscope, and M. Genova for assistance with the FACSort.

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  1. Matthew L. Albert and Jong-Ii Kim: These authors contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Neuro-Oncology, Rockefeller University , 1230 York Avenue, Box 226

    Matthew L. Albert

  2. New York, 10021, USA

    Matthew L. Albert

  3. Department of Biochemistry and Molecular Biology, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, Newark, 07214, New Jersey, USA

    Jong-Ii Kim & Raymond B. Birge

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  1. Matthew L. Albert
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Correspondence to Matthew L. Albert or Raymond B. Birge.

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Albert, M., Kim, JI. & Birge, R. αvβ5 integrin recruits the CrkII–Dock180–Rac1 complex for phagocytosis of apoptotic cells. Nat Cell Biol 2, 899–905 (2000). https://doi.org/10.1038/35046549

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