GPR39 activation inhibits AQP2 trafficking and alters cytoskeletal organization.

ABSTRACT: G protein-coupled receptor 39 (GPR39) is an orphan receptor that is highly expressed in renal collecting duct principal cells. GPR39 activation in vivo leads to reduced urinary concentration capacity. In this study, we used mpkCCD cells, a model of principal cells in the collecting duct, to examine the cell biological effects of GPR39 activation. Pharmacological activation of GPR39 with the synthetic agonist cpd1324 impaired vasopressin-mediated aquaporin-2 (AQP2) apical trafficking and reduced total AQP2 expression following long-term treatment, consistent with its known in vivo role. These effects were absent in GPR39 knockout cells. In addition, GPR39 activation altered apical membrane morphology, disrupted the tight junction network, and reduced cortical F-actin expression, suggesting

SUBMITTER: Kui MK 

PROVIDER: S-EPMC12863663 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature