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

Published on: December 27, 2016

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p85α recruitment by the CD300f phosphatidylserine receptor mediates apoptotic cell clearance required for

Linjie Tian1, Seung-Chul Choi1, Yousuke Murakami2

  • 11] Receptor Cell Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA [2].

Nature Communications
|January 31, 2014
PubMed

Insights

Mouse CD300f protein recognizes phosphatidylserine on apoptotic cells, regulating their clearance. This process is crucial for immune homeostasis and preventing autoimmune diseases like lupus.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Apoptotic cell clearance is vital for maintaining immune homeostasis.
  • Dysfunctional clearance contributes to autoimmune diseases.
  • The role of CD300f in apoptotic cell phagocytosis was previously unclear.

Purpose of the Study:

  • To elucidate the mechanism by which CD300f regulates apoptotic cell clearance.
  • To investigate the role of CD300f phosphorylation in phagocytosis.
  • To determine the in vivo consequences of CD300f deficiency on immune homeostasis and autoimmunity.

Main Methods:

  • Utilized mouse models and primary macrophages.
  • Investigated protein-protein interactions using biochemical assays.
  • Analyzed signaling pathways including PI3K, Rac/Cdc42, and F-actin dynamics.
  • Assessed phagocytosis of apoptotic cells in vitro and in vivo.

Main Results:

  • CD300f directly recognizes phosphatidylserine on apoptotic cells.
  • Phosphorylation of CD300f, particularly at Y276, is essential for efficient phagocytosis.
  • CD300f recruits and activates PI3K, leading to Rac/Cdc42 activation and F-actin remodeling.
  • CD300f-deficient macrophages exhibit impaired apoptotic cell clearance.
  • Absence of CD300f accelerates the development of lupus-like autoimmune disease.

Conclusions:

  • CD300f acts as a key regulator of apoptotic cell phagocytosis through a PI3K-dependent pathway.
  • Proper apoptotic cell clearance mediated by CD300f is critical for preventing autoimmunity.
  • CD300f is a significant factor in maintaining immune homeostasis.

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