Phosphorylation of distal C-terminal residues promotes TRPV4 channel activation in response to arachidonic acid

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108260 - 108260

Published: Feb. 1, 2025

Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+-permeable channel activated by diverse physical and chemical stimuli, including mechanical stress endogenous lipid arachidonic acid (AA) its metabolites. Phosphorylation of TRPV4 protein kinase A (PKA) C (PKC) predominant mechanism for regulation, especially in the cytoplasmic domains due to their importance assembly, channelopathies. However, studies corresponding phosphorylation sites these kinases remain incomplete. We investigated role Ser-823 residue as site regulating activity agonist-induced activation. Using mass spectrometry, we identified new confirmed previously known Ser-824 C-terminal tail. The low level at was stimulated PKC lesser extent PKA human coronary artery endothelial cells (HCAECs) embryonic kidney 293 (HEK 293) cells. AA-induced activation enhanced phosphomimetic S823E but blunted S823A/S824A mutants, whereas synthetic agonist GSK1016790A unaffected. Further, AA not or abolished inhibitor alone combination with inhibitor, respectively. computational modeling, refined proposed structural model regulation phosphorylation. Together, results provide insight into how stimuli-specific regulated discrete residues (e.g., Ser-824) channel.

Language: Английский

TRPV4 activation by core body temperature has multimodal functions in the central nervous system

The Journal of Physiological Sciences, Journal Year: 2024, Volume and Issue: 74(1)

Published: Nov. 22, 2024

Abstract Brain temperature is strictly regulated by various endogenous mechanisms and significantly contributes to brain function in homeothermic animals, making it an important factor for health. Thermosensitive transient receptor potential (TRP) channels convert information into electrical signals through cation influx. In particular, TRPV4 involved the regulation of function. TRPV4, constitutively active neurons its activation temperature, increases neuronal firing. TRPV4KO mice have electroencephalogram abnormalities, resulting depression-like social behavioral abnormalities. This basic as a translator information, has been implicated several diseases, including epilepsy stress-induced depression. addition functions, many key functions glia vasculature that depend on contribute activity. this review, I summarize importance activities relation focus how hyperthermia-induced dysfunction exacerbates diseases.

Language: Английский

Roles for TRPV4 in disease: A discussion of possible mechanisms.

Cell Calcium, Journal Year: 2024, Volume and Issue: unknown, P. 102972 - 102972

Published: Nov. 1, 2024

Language: Английский