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.

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.

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.

Our findings suggest that CILK1 deficiency in renal collecting ducts leads to PKD and promotes ciliary trafficking via increased KLC3.

纤毛发生相关激酶 1 ( CILK1 ) 是一种纤毛基因，位于初级纤毛中并调节纤毛运输。CILK1突变会导致各种纤毛病。然而，CILK1 缺陷型肾病的发病机制尚不清楚。

为了检查 CILK1 缺乏是否会导致 PKD 并伴有纤毛异常，我们培育了肾集合管细胞中Cilk1缺失的小鼠。使用酵母双杂交系统和共免疫沉淀 (co-IP) 来鉴定Cilk1缺陷模型中纤毛运输和囊肿进展的新型调节剂驱动蛋白轻链-3 (KLC3)。使用免疫细胞化学和 co-IP 来检查 KLC3 对 IFT-B 复合物和 EGFR 纤毛运输的影响。我们通过调节 CILK1 和 KLC3 表达水平评估了这些基因对纤毛运输和囊肿进展的影响。

CILK1 缺陷会导致 PKD 并伴有异常的纤毛运输。KLC3 在纤毛基部与 CILK1 相互作用，并且在 CILK1 缺陷小鼠的囊肿衬里细胞中增加。在 CILK1 缺乏的情况下，KLC3 过表达会促进 IFT-B 和 EGFR 的纤毛募集，从而导致囊肿发生过程中的纤毛缺陷。KLC3 的减少挽救了纤毛缺陷并抑制了 CILK1 缺陷引起的囊肿进展。

我们的研究结果表明，肾集合管中的 CILK1 缺乏会导致 PKD，并通过增加 KLC3 促进纤毛运输。