KLC3 Regulates Ciliary Trafficking and Cyst Progression in CILK1 Deficiency–Related Polycystic Kidney Disease

Gyuyeong Rah, Hwayeon Cha, Joohee Kim, Jieun Song, Hyunho Kim, Yun Kyu Oh, Curie Ahn, Minyong Kang, Jongmin Kim, Kyung Hyun Yoo, Min Jung Kim, Hyuk Wan Ko, Je Yeong Ko, Jong Hoon Park

Research output: Contribution to journalArticlepeer-review


Background Ciliogenesis-associated kinase 1 (CILK1) is a ciliary gene that localizes in primary cilia and regulates ciliary transport. Mutations in CILK1 cause various ciliopathies. However, the pathogenesis of CILK1-deficient kidney disease is unknown. Methods To examine whether CILK1 deficiency causes PKD accompanied by abnormal cilia, we generated mice with deletion of Cilk1 in cells of the renal collecting duct. A yeast two-hybrid system and coimmunoprecipitation (co-IP) were used to identify a novel regulator, kinesin light chain–3 (KLC3), of ciliary trafficking and cyst progression in the Cilk1-deficient model. Immunocytochemistry and co-IP were used to examine the effect of KLC3 on ciliary trafficking of the IFT-B complex and EGFR. We evaluated the effects of these genes on ciliary trafficking and cyst progression by modulating CILK1 and KLC3 expression levels. Results CILK1 deficiency leads to PKD accompanied by abnormal ciliary trafficking. KLC3 interacts with CILK1 at cilia bases and is increased in cyst-lining cells of CILK1-deficient mice. KLC3 overexpression promotes ciliary recruitment of IFT-B and EGFR in the CILK1 deficiency condition, which contributes to the ciliary defect in cystogenesis. Reduction in KLC3 rescued the ciliary defects and inhibited cyst progression caused by CILK1 deficiency. Conclusions Our findings suggest that CILK1 deficiency in renal collecting ducts leads to PKD and promotes ciliary trafficking via increased KLC3.

Original languageEnglish
Pages (from-to)1726-1741
Number of pages16
JournalJournal of the American Society of Nephrology
Issue number9
Publication statusPublished - 2022 Sept

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Copyright © 2022 by the American Society of Nephrology.

All Science Journal Classification (ASJC) codes

  • Nephrology


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