Efferocytosis requires periphagosomal Ca 2+ -signaling and TRPM7-mediated electrical activity.

Autor: Schappe MS; Pharmacology Department, University of Virginia, Pinn Hall, 1340 Jefferson Park Avenue, Charlottesville, VA, 22908, USA.; Department of Cell Biology, Harvard Medical School, Boston, MA, USA., Stremska ME; Pharmacology Department, University of Virginia, Pinn Hall, 1340 Jefferson Park Avenue, Charlottesville, VA, 22908, USA., Busey GW; Pharmacology Department, University of Virginia, Pinn Hall, 1340 Jefferson Park Avenue, Charlottesville, VA, 22908, USA., Downs TK; Pharmacology Department, University of Virginia, Pinn Hall, 1340 Jefferson Park Avenue, Charlottesville, VA, 22908, USA., Seegren PV; Pharmacology Department, University of Virginia, Pinn Hall, 1340 Jefferson Park Avenue, Charlottesville, VA, 22908, USA., Mendu SK; Pharmacology Department, University of Virginia, Pinn Hall, 1340 Jefferson Park Avenue, Charlottesville, VA, 22908, USA., Flegal Z; Pharmacology Department, University of Virginia, Pinn Hall, 1340 Jefferson Park Avenue, Charlottesville, VA, 22908, USA., Doyle CA; Pharmacology Department, University of Virginia, Pinn Hall, 1340 Jefferson Park Avenue, Charlottesville, VA, 22908, USA., Stipes EJ; Pharmacology Department, University of Virginia, Pinn Hall, 1340 Jefferson Park Avenue, Charlottesville, VA, 22908, USA., Desai BN; Pharmacology Department, University of Virginia, Pinn Hall, 1340 Jefferson Park Avenue, Charlottesville, VA, 22908, USA. bdesai@virginia.edu.; Carter Immunology Center, University of Virginia, 345 Crispell Dr. MR-6, Charlottesville, VA, 22908, USA. bdesai@virginia.edu.; Robert M. Berne Cardiovascular Research Center, University of Virginia, 415 Lane Rd, Charlottesville, VA, 22908, USA. bdesai@virginia.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Jun 09; Vol. 13 (1), pp. 3230. Date of Electronic Publication: 2022 Jun 09.
DOI: 10.1038/s41467-022-30959-4
Abstrakt: Efficient clearance of apoptotic cells by phagocytosis, also known as efferocytosis, is fundamental to developmental biology, organ physiology, and immunology. Macrophages use multiple mechanisms to detect and engulf apoptotic cells, but the signaling pathways that regulate the digestion of the apoptotic cell cargo, such as the dynamic Ca 2+ signals, are poorly understood. Using an siRNA screen, we identify TRPM7 as a Ca 2+ -conducting ion channel essential for phagosome maturation during efferocytosis. Trpm7-targeted macrophages fail to fully acidify or digest their phagosomal cargo in the absence of TRPM7. Through perforated patch electrophysiology, we demonstrate that TRPM7 mediates a pH-activated cationic current necessary to sustain phagosomal acidification. Using mice expressing a genetically-encoded Ca 2+ sensor, we observe that phagosome maturation requires peri-phagosomal Ca 2+ -signals dependent on TRPM7. Overall, we reveal TRPM7 as a central regulator of phagosome maturation during macrophage efferocytosis.
(© 2022. The Author(s).)
Databáze: MEDLINE
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