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alphavbeta5 integrin recruits the CrkII-Dock180-rac1 complex for phagocytosis of apoptotic cells

M L Albert1, J I Kim, R B Birge

  • 1Laboratory of Neuro-Oncology, Rockefeller University, 1230 York Avenue, Box 226 New York 10021, USA.

Nature Cell Biology
|January 9, 2001
PubMed

Insights

The integrin alphavbeta5 receptor mediates both binding and internalization of apoptotic cells. This process involves a conserved signaling pathway crucial for cellular clearance.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • Integrin receptors play a role in the phagocytosis of apoptotic cells.
  • The specific function of integrins in mediating the internalization of apoptotic cells remains largely unknown.
  • Previous studies primarily used blocking antibodies, limiting understanding of integrin-mediated internalization.

Purpose of the Study:

  • To elucidate the role of the alphavbeta5 integrin receptor in the binding and internalization of apoptotic cells.
  • To identify the signaling pathways involved in integrin-mediated apoptotic cell clearance.
  • To establish functional analogies between C. elegans and human cell signaling complexes in phagocytosis.

Main Methods:

  • Investigated the function of the alphavbeta5 receptor in apoptotic cell uptake.
  • Analyzed signaling pathways downstream of alphavbeta5 engagement.
  • Utilized molecular complex recruitment assays and Rac1 activation studies.
  • Compared mammalian signaling complexes with Caenorhabditis elegans (C. elegans) pathways.

Main Results:

  • The alphavbeta5 receptor mediates both the binding and internalization of apoptotic cells.
  • Internalization is dependent on signaling through the beta5 cytoplasmic tail.
  • Engagement of alphavbeta5 recruits the p130cas-CrkII-Dock180 complex, activating Rac1 and promoting phagosome formation.
  • Identified a conserved signaling pathway linking alphavbeta5 to CED-2-CED-5-CED-10 homologs in human cells.

Conclusions:

  • Integrin-receptor signaling is critical for the internalization of apoptotic material.
  • The CED-2-CED-5-CED-10 complex in C. elegans is functionally analogous to the CrkII-Dock180-Rac1 complex in mammalian cells.
  • Revealed an evolutionarily conserved pathway for apoptotic cell recognition and internalization by various cell types.

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