The vanilloid transient receptor potential channel TRPV4: from structure to disease.
The Transient Receptor Potential Vanilloid 4 channel, TRPV4, is a Ca(2+) and Mg(2+) permeable non-selective cation channel involved in many different cellular functions. It is activated by a variety of physical and chemical stimuli, including heat, mechano-stimuli, endogenous substances such as arachidonic acid and its cytochrome P450-derived metabolites (epoxyeicosatrienoic acids), endocannabinoids (anandamide and 2-arachidonoylglycerol), as well as synthetic alpha-phorbol derivatives. Recently, TRPV4 has been characterized as an important player modulating osteoclast differentiation in bone remodelling and as a urothelial mechanosensor that controls normal voiding. Several TRPV4 gain-of-function mutations are shown to cause autosomal-dominant bone dysplasias such as brachyolmia and Koszlowski disease. In this review we comprehensively describe the structural, biophysical and (patho)physiological properties of the TRPV4 channel and we summarize the current knowledge about the role of TRPV4 in the pathogenesis of several diseases.
Everaerts
Wouter
W
Department of Molecular Cell Biology, Laboratory Ion Channel Research, Campus Gasthuisberg, KULeuven, Herestraat 49, bus 802, B-3000 Leuven, Belgium.
Nilius
Bernd
B
Owsianik
Grzegorz
G
D000818:Animals; D001847:Bone Diseases / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D050916:TRPV Cation Channels / Q000737:chemistry* / Q000378:metabolism*; D050051:Transient Receptor Potential Channels / Q000502:physiology*; D001745:Urinary Bladder Diseases / Q000378:metabolism* / Q000473:pathology
D050916:TRPV Cation Channels; C416986:TRPV4 protein, human; D050051:Transient Receptor Potential Channels; C486576:Trpv4 protein, mouse