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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Migration to apoptotic "find-me" signals is mediated via the phagocyte receptor G2A

Christoph Peter1, Michaela Waibel, Caius G Radu

  • 1Department of Internal Medicine I, University of Tuebingen, 72076 Tuebingen, Germany.

The Journal of Biological Chemistry
|December 20, 2007
PubMed

Insights

Lysophosphatidylcholine (lysoPC) acts as a crucial "find-me" signal attracting phagocytes to clear apoptotic cells. The G2A receptor mediates this process, preventing inflammation and autoimmunity.

Area of Science:

  • Cellular Biology
  • Immunology
  • Biochemistry

Background:

  • Phagocytosis of apoptotic cells is vital for preventing secondary necrosis and subsequent inflammation.
  • Dying cells release signals to attract phagocytes, but key molecular players remain unidentified.
  • Lysophospholipids (lysoPLs) are hypothesized find-me signals, but their specific identity and receptors are largely unknown.

Purpose of the Study:

  • To identify the specific lysophospholipid (lysoPL) acting as an apoptotic cell attraction signal.
  • To determine the phagocyte receptor responsible for recognizing this signal.
  • To elucidate the molecular mechanism underlying phagocyte chemotaxis towards apoptotic cells.

Main Methods:

  • Detailed structural analysis of lysophospholipids and their metabolites.
  • RNA interference (RNAi) studies to assess gene function.
  • Expression analysis of G-protein-coupled receptors in monocytic cells.

Main Results:

  • Lysophosphatidylcholine (lysoPC), not its metabolites or other lysoPLs, was identified as the essential apoptotic attraction signal.
  • The G-protein-coupled receptor G2A was shown to be involved in the chemotaxis of monocytic cells towards apoptotic cells.
  • G2A, but not GPR4, plays a critical role in this phagocytic process.

Conclusions:

  • Lysophosphatidylcholine (lysoPC) is the primary "find-me" signal released by apoptotic cells.
  • The G2A receptor is the crucial receptor mediating phagocyte attraction to apoptotic cells.
  • This lysoPC-G2A system is essential for efficient apoptotic cell clearance and prevention of autoimmunity.

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