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Engulfment of apoptotic cells in C. elegans is mediated by integrin alpha/SRC signaling

Tsung-Yuan Hsu1, Yi-Chun Wu

  • 1Institute of Molecular and Cellular Biology, National Taiwan University, Number 1, Section 4, Roosevelt Road, Taipei 10617, Taiwan.

Current Biology : CB
|March 16, 2010
PubMed
Abstract

Insights

Integrin acts as an engulfment receptor in C. elegans, facilitating the removal of apoptotic cells. This process involves SRC-1 kinase, linking integrin signaling to the CED-2/CrkII-CED-5/Dock180-CED-12/ELMO complex for efficient cell corpse clearance.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Molecular Biology

Background:

  • Apoptotic cell engulfment is crucial for maintaining tissue homeostasis and organism development.
  • Multiple engulfment receptors signal through the conserved CED-2/CrkII-CED-5/Dock180-CED-12/ELMO pathway for efficient cell corpse removal.
  • The specific identities of upstream engulfment receptors, beyond PSR-1, remained largely unknown.

Purpose of the Study:

  • To identify novel engulfment receptors involved in apoptotic cell removal in C. elegans.
  • To elucidate the signaling pathway linking engulfment receptors to the conserved CED-2/CrkII-CED-5/Dock180-CED-12/ELMO complex.
  • To investigate the role of integrin and associated kinases in the phagocytosis of apoptotic cells.

Main Methods:

  • Genetic analysis of integrin alpha gene (ina-1) mutants to assess engulfment efficiency.
  • In vivo binding assays using the INA-1 extracellular domain to detect apoptotic cell surfaces.
  • Co-localization studies of INA-1 and SRC-1 in phagocytic cups.
  • Biochemical interaction studies to map signaling connections.

Main Results:

  • Integrin (INA-1) functions as an engulfment receptor, mediating recognition and phagocytosis of apoptotic cells in C. elegans.
  • Mutations in ina-1 lead to defective engulfment of apoptotic cells.
  • INA-1 binding to apoptotic cells requires the phospholipid scramblase SCRM-1 for phosphatidylserine exposure.
  • The nonreceptor tyrosine kinase SRC-1 is essential for INA-1-mediated engulfment and relays signals to the CED-2/CrkII-CED-5/Dock180-CED-12/ELMO complex.
  • SRC-1 interacts with CED-2 and the INA-1 cytoplasmic domain, promoting CED-10/Rac activation and apoptotic cell internalization.

Conclusions:

  • Integrin acts as a key engulfment receptor at the whole-organism level.
  • A novel signaling pathway is revealed where SRC-1 provides a FAK-independent link between integrin alpha and the CED-2/CrkII-CED-5/Dock180-CED-12/ELMO module.
  • This pathway is critical for promoting the internalization of apoptotic cells during development and homeostasis.

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