Adenylyl cyclase 5 links changes in calcium homeostasis to cAMP-dependent cyst growth in polycystic liver disease.

ABSTRACT:

Background & aims

Genetic defects in polycystin-1 or -2 (PC1 or PC2) cause polycystic liver disease associated with autosomal dominant polycystic kidney disease (PLD-ADPKD). Progressive cyst growth is sustained by a cAMP-dependent Ras/ERK/HIFα pathway, leading to increased vascular endothelial growth factor A (VEGF-A) signaling. In PC2-defective cholangiocytes, cAMP production in response to [Ca²⁺]_ER depletion is increased, while store-operated Ca²⁺ entry (SOCE), intracellular and endoplasmic reticulum [Ca²⁺]_ER levels are reduced. We investigated whether the adenylyl cyclases, AC5 and AC6, which can be inhibited by Ca²⁺, are activated by the ER chaperone STIM1. This would result in cAMP/PKA-dependent Ras/ERK/HIFα pat

SUBMITTER: Spirli C 

PROVIDER: S-EPMC5316496 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature