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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

Journey to the grave: signaling events regulating removal of apoptotic cells

Jason M Kinchen1, Kodi S Ravichandran

  • 1Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908, USA.

Journal of Cell Science
|June 27, 2007
PubMed

Insights

Programmed cell death involves engulfing dead cells. New proteins link corpse recognition to membrane movement, facilitating cell removal and an anti-inflammatory state.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Immunology

Background:

  • Programmed cell death (apoptosis) is essential for development and daily cell turnover.
  • Efficient removal of apoptotic cells by phagocytes is crucial for tissue homeostasis.
  • The molecular mechanisms of apoptotic cell engulfment are under active investigation.

Purpose of the Study:

  • To elucidate the molecular players and signaling pathways involved in apoptotic cell engulfment.
  • To identify novel proteins that mediate the recognition and internalization of apoptotic cells.
  • To understand how apoptotic cell recognition influences the phagocyte's inflammatory response.

Main Methods:

  • Review of recent studies identifying conserved proteins in the engulfment pathway.
  • Analysis of signaling modules involving CED-12/ELMO, CED-5/Dock180, CED-1/LRP1, and CED-6/GULP.
  • Examination of the impact of apoptotic cell recognition on phagocyte cytokine secretion.

Main Results:

  • Identified two key signaling modules: CED-12/ELMO-CED-5/Dock180 (a Rac1 GEF) and CED-1/LRP1-CED-6/GULP.
  • Demonstrated that apoptotic cell recognition by phagocytes induces an anti-inflammatory cytokine profile.
  • Highlighted the role of specific proteins in linking corpse recognition to membrane dynamics for efficient internalization.

Conclusions:

  • Recent discoveries have molecularly delineated the phagocytic process for apoptotic cells.
  • Novel signaling proteins provide a framework for understanding corpse recognition and engulfment.
  • Phagocyte response to apoptotic cells is characterized by an anti-inflammatory state, distinct from necrotic cell responses.

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