Chanzyme TRPM7 Mediates the Ca²⁺ Influx Essential for Lipopolysaccharide-Induced Toll-Like Receptor 4 Endocytosis and Macrophage Activation.

ABSTRACT: Toll-like receptors (TLRs) sense pathogen-associated molecular patterns to activate the production of inflammatory mediators. TLR4 recognizes lipopolysaccharide (LPS) and drives the secretion of inflammatory cytokines, often contributing to sepsis. We report that transient receptor potential melastatin-like 7 (TRPM7), a non-selective but Ca²⁺-conducting ion channel, mediates the cytosolic Ca²⁺ elevations essential for LPS-induced macrophage activation. LPS triggered TRPM7-dependent Ca²⁺ elevations essential for TLR4 endocytosis and the subsequent activation of the transcription factor IRF3. In a parallel pathway, the Ca²⁺ signaling initiated by TRPM7 was also essential for the nuclear translocation of NFκB. Consequently, TRPM7-deficient macrophag

SUBMITTER: Schappe MS 

PROVIDER: S-EPMC5783319 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature