Nek1 regulation of VHL and cilia

Abstract

Nek1 is a member of NIMA related kinases in mammals that has been known to regulate ciliogenesis. Loss of function mutation in Nek1 leads to polycystic kidney disease in mouse and renal cysts in humans. pVHL, a well known tumor suppressor, has been recently implicated in the regulation of cilia and cell cycle. Loss of VHL function leads to renal cystic disease and renal cell carcinoma. Since mutation of Nek1 and VHL results in similar phenotype, we investigated if Nek1 and pVHL might function in a common regulatory pathway. Our in vitro and in vivo experiments show that pVHL may be a substrate of Nek1. Phosphorylation of VHL by Nek1 may affect the stability of pVHL and cilia dynamics. Phosphorylation site mutations in pVHL results in higher stability. Cells expressing mutant pVHL have stable cilia, resistant to serum stimulation and Nocodazole treatment. Phosphorylation of VHL by Nek1 does not seem to affect hypoxia inducible factors (HIF). Together, the results reveal a novel regulation of pVHL by Nek1, which may contributes to the regulation of cilia.This study was supported by NIH