Journal of cell science
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Journal of cell science · Feb 2017
Role of the phagosomal redox-sensitive TRP channel TRPM2 in regulating bactericidal activity of macrophages.
Acidification of macrophage phagosomes serves an important bactericidal function. We show here that the redox-sensitive transient receptor potential (TRP) cation channel TRPM2 is expressed in the phagosomal membrane and regulates macrophage bactericidal activity through the activation of phagosomal acidification. Measurement of the TRPM2 current in phagosomes identified TRPM2 as a functional redox-sensitive cation channel localized in the phagosomal membrane. ⋯ Trpm2(+/+) macrophages treated with the vacuolar H(+)-ATPase inhibitor bafilomycin showed reduced bacterial clearance, similar to that in Trpm2(-/-) macrophages. Direct activation of TRPM2 using adenosine diphosphate ribose (ADPR) induced both phagosomal acidification and bacterial killing. These data collectively demonstrate that TRPM2 regulates phagosomal acidification, and is essential for the bacterial killing function of macrophages.