pH regulation and beyond: unanticipated functions for the voltage-gated proton channel, HVCN1.
Electrophysiological studies have implicated voltage-gated proton channels in several specific cellular contexts. In neutrophils, they mediate charge compensation that is associated with the oxidative burst of phagocytosis. Molecular characterization of the hydrogen voltage-gated channel 1 (HVCN1) has enabled identification of unanticipated and diverse functions: HVCN1 not only modulates signaling from the B-cell receptor following B-cell activation and histamine release from basophils, but also mediates pH-dependent activation of spermatozoa, as well as acid secretion by tracheal epithelium. The importance of HVCN1 in pH regulation during phagocytosis was established by surprising evidence that indicated its first-responder role. In this review, we discuss recent findings from a functional perspective, and the potential of HVCN1 as a therapeutic target for autoimmune and other diseases.
Centre for Cancer & Inflammation, Institute of Cancer, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, United Kingdom. m.capasso@qmul.ac.uk
Melania
M
Capasso
Thomas E
TE
DeCoursey
Martin J S
MJ
Dyer
D000818:Animals; D001491:Basophils; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008297:Male; D010587:Phagocytosis; D011947:Receptors, Antigen, B-Cell; D015398:Signal Transduction; D013094:Spermatozoa / Q000378:metabolism
C510235:HVCN1 protein, human; D007473:Ion Channels; D011947:Receptors, Antigen, B-Cell