Polycystin 1 ciliary localization is regulated by its aGPCR activity
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) develops due to loss of function mutations in the PKD1 and PKD2 genes, which encode PC1 and PC2, respectively. PC1 is a 460kD multi‐spanning membrane protein that undergoes multiple proteolytic cleavages, at least two of which release C‐terminal fragments. Polycystin 1 and Polycystin 2 both prominently localize to the primary cilium where they contribute to cellular mechano‐sensation and also form a cation‐permeable heterotetrameric channel that may contribute to Ca2+ flux into the cilia. Recent studies demonstrate that PC1 can function as an atypical adhesion GPCR that is activated by Wnt ligands. Wnt ligand binding leads to dissociation of the PC1 extracellular N terminal fragment and allows the PC1 receptor function to be activated by a tethered agonist peptide that resides at the N terminus of the PC1 transmembrane domains.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 01, 2022
- Source ID
- 10.1096/fasebj.2022.36.s1.r4689
Entities
People
- Michael J Caplan
- Nikolay Gresko
Organizations
- Congressionally Directed Medical Research Programs
- National Institutes of Health
- Yale University