KLC3 regulates axonemal glutamylation via RAB11/FIP5 in polycystic kidney disease.

KLC3 was identified as a novel ciliary gene in a previous study that caused cyst formation due to abnormal ciliary defects in cyst-lining cells of polycystic kidney disease (PKD) models. RAB11FIP5 is a regulator of tubulin post-translational modification (PTM) in primary cilia and is located on basal bodies. Here, we determined the relationship between KLC3 and RAB11FIP5 mediated tubulin PTM, which may be involved in cyst progression in patients with PKD. KLC3 co-localizes and interacts with RAB11FIP5 around the basal bodies of primary cilia. KLC3 regulates axonemal glutamylation accompanied by changes in RAB11FIP5 expression in basal bodies, which may be involved in anterograde ciliary trafficking. Similarly, in previous KLC3 results, increased RAB11FIP5 and axonemal glutamylation were observed in the cyst-lining cells of PKD. When the increased KLC3 in ADPKD patient-derived cells decreased, not only ciliary glutamylation and IFT88, but also cell proliferation decreased. Our findings suggest that KLC3 regulates ciliary glutamylation mediated by RAB11FIP5 and it may contribute to cyst progression in PKD.