Efferocytosis Requires Periphagosomal Ca-signaling and TRPM7-mediated Electrical Activity

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Jun 10

PMID 35680919

Authors

Michael S Schappe

Marta E Stremska

Gregory W Busey

Taylor K Downs

Philip V Seegren

Suresh K Mendu

Zachary Flegal

Catherine A Doyle

Eric J Stipes

Bimal N Desai

Affiliations

Soon will be listed here.

Abstract

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 signals, are poorly understood. Using an siRNA screen, we identify TRPM7 as a Ca-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 sensor, we observe that phagosome maturation requires peri-phagosomal Ca-signals dependent on TRPM7. Overall, we reveal TRPM7 as a central regulator of phagosome maturation during macrophage efferocytosis.

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