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J Biol Chem 2019 Nov 29;29448:18421-18434. doi: 10.1074/jbc.RA119.011187.
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Volume sensing in the transient receptor potential vanilloid 4 ion channel is cell type-specific and mediated by an N-terminal volume-sensing domain.

Toft-Bertelsen TL , Yarishkin O , Redmon S , Phuong TTT , Križaj D , MacAulay N .

Many retinal diseases are associated with pathological cell swelling, but the underlying etiology remains to be established. A key component of the volume-sensitive machinery, the transient receptor potential vanilloid 4 (TRPV4) ion channel, may represent a sensor and transducer of cell swelling, but the molecular link between the swelling and TRPV4 activation is unresolved. Here, our results from experiments using electrophysiology, cell volumetric measurements, and fluorescence imaging conducted in murine retinal cells and Xenopus oocytes indicated that cell swelling in the physiological range activated TRPV4 in Müller glia and Xenopus oocytes, but required phospholipase A2 (PLA2) activity exclusively in Müller cells. Volume-dependent TRPV4 gating was independent of cytoskeletal rearrangements and phosphorylation. Our findings also revealed that TRPV4-mediated transduction of volume changes are defined by its N terminus, more specifically by its distal-most part. We conclude that the volume sensitivity and function of TRPV4 in situ depends critically on its functional and cell type-specific interactions.

PubMed ID: 31619514
PMC ID: PMC6885641
Article link: J Biol Chem
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: aqp4 lat pla2g1b prkg1 trpv1 trpv4
GO keywords: phospholipase A2 activity [+]

Disease Ontology terms: glaucoma

Article Images: [+] show captions
References [+] :
Ackerman, Hypotonicity activates a native chloride current in Xenopus oocytes. 1994, Pubmed, Xenbase