Klc3 Regulates Ciliary Trafficking and Cyst Formation in Kidney Epithelial Cells

Background: Primary cilia are microtubule-based organelles that extends from the cell membrane and function as biosensor to regulate intracellular signaling pathways. As primary cilia cannot synthesis proteins by themselves, trafficking of ciliary protein via the process of intraflagellar transport (IFT) is crucial for cilia maintenance and function. Methods: Immunocytochemistry and co-IP were used to examine the effect of kinesin light chain-3 (Klc3) in ciliary trafficking. By modulating Klc3 expression levels, we evaluated the effect of Klc3 in ciliary trafficking and in vitro cyst formation. Results: We identified Klc3 as ciliary trafficking regulator of kidney epithelial cells. Klc3 localized to adjacent to basal body of cilia and regulated ciliary IFT recruitments by interacting with IFT-B core-2 complex via its tetratricopeptide-repeat (TPR) domains. Also, Klc3 overexpression increased in vitro cyst formation of kidney epithelial cells, whereas suppression of Klc3 relieved in vitro cyst enlargement induced by Pkd1 or Pkd2 deficiency. In support our findings, ciliopathy models such as human ADPKD and animal PKD models with ciliary IFT accumulations had an increased Klc3 expression. Conclusion: We provide conclusive evidences of KLC3 roles for regulating ciliary IFT recruitment and cyst formation in kidney epithelial cells. Funding: Government Support – Non-U.S.