Efferocytosis requires periphagosomal Ca2+-signaling and TRPM7-mediated electrical activity

Michael S Schappe1,2, Marta E Stremska1, Gregory W Busey1

  • 1Pharmacology Department, University of Virginia, Pinn Hall, 1340 Jefferson Park Avenue, Charlottesville, VA, 22908, USA.

Nature Communications
|June 10, 2022
PubMed

Insights

TRPM7 is a calcium channel crucial for macrophage efferocytosis, enabling the digestion of engulfed apoptotic cells. This study identifies TRPM7

Area of Science:

  • Immunology
  • Cell Biology
  • Physiology

Background:

  • Efficient efferocytosis (clearance of apoptotic cells) is vital for tissue homeostasis and immune function.
  • Macrophages engulf apoptotic cells, but the mechanisms regulating the digestion of this cargo, particularly calcium signaling, remain unclear.

Purpose of the Study:

  • To identify molecular players regulating phagosome maturation during efferocytosis.
  • To elucidate the role of calcium signaling in the digestion of apoptotic cargo by macrophages.

Main Methods:

  • siRNA screening to identify key genes in efferocytosis.
  • Perforated patch electrophysiology to study ion channel function.
  • Genetically-encoded calcium sensors in mice to visualize peri-phagosomal calcium dynamics.

Main Results:

  • TRPM7, a calcium-conducting ion channel, was identified as essential for phagosome maturation.
  • Macrophages lacking TRPM7 showed impaired phagosomal acidification and cargo digestion.
  • TRPM7 mediates a pH-activated current vital for phagosomal acidification.
  • Phagosome maturation is dependent on TRPM7-mediated peri-phagosomal calcium signals.

Conclusions:

  • TRPM7 is a critical regulator of phagosome maturation during macrophage efferocytosis.
  • TRPM7's ion channel activity is necessary for the complete digestion of apoptotic cells.

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