CDKL kinase regulates the length of the ciliary proximal segment
CDKL kinase regulates the length of the ciliary proximal segment
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DOI：
10.1016/j.cub.2021.03.068
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发表时间：
2021-06-07
期刊：
影响因子：
9.2
通讯作者：
Leroux，Michel R.
中科院分区：
文献类型：
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作者：
Park，Kwangjin;Li，Chunmei;Leroux，Michel R.
纤毛是存在于大多数单细胞真核生物和不同后生动物细胞类型中的细胞器。为了完成它们在细胞运动、流体流动和信号传递中的重要作用，纤毛被分成不同的结构、组成和功能的亚室。这些特定的小舱是如何建造的，几乎完全没有人探索。在这里，我们发现了与人CDKL激酶家族(CDKL1/CDKL2/CDKL3/CDKL4/CDKL5)相关的c.CDKL-1，它特异性地控制着近端的长度，这是一个从四膜虫纤毛进化而来的纤毛亚结构域。CDKL-1与鞭毛内转运(IFT)相关，影响IFT顺行运动异源三聚体kinesin-II和同源二聚体OSM-3-kinesin/KIF17在近段的分布，并移位近段和远段之间的边界(PS/DS边界)。CDKL-1似乎独立于几个影响纤毛长度的因素发挥作用，即DYF-5(哺乳动物的CILK1/MAK)和NEKL-1(NEK9)，以及解聚运动蛋白KLP-13(KIF19)和KLP-7(KIF2)。然而，CDKL-1的正确定位和功能需要不同的激酶DYF-18(CCRK)，并且类似地影响近端片段的长度。CDKL-1的缺失在不损害纤毛微管整体结构完整性的情况下影响近段长度，也损害纤毛依赖的过程，即cGMP信号依赖的体长控制和二氧化碳避免。总之，我们的发现表明纤毛长度受不同的途径调节，IFT相关的激酶CDKL-1对于构建特定的纤毛室是必不可少的，并有助于发育和感觉生理学。
Cilia are organelles found throughout most unicellular eukaryotes and different metazoan cell types. To accomplish their essential roles in cell motility, fluid flow, and signaling, cilia are divided into subcompartments with variable structures, compositions, and functions. How these specific subcompartments are built remains almost completely unexplored. Here, we show thatC. elegansCDKL-1, related to the human CDKL kinase family (CDKL1/CDKL2/CDKL3/CDKL4/CDKL5), specifically controls the length of the proximal segment, a ciliary subdomain conserved in evolution fromTetrahymenamotile cilia toC. eleganschemosensory, mammalian olfactory, and photoreceptor non-motile cilia. CDKL-1 associates with intraflagellar transport (IFT), influences the distribution of the IFT anterograde motors heterotrimeric kinesin-II and homodimeric OSM-3-kinesin/KIF17 in the proximal segment, and shifts the boundary between the proximal and distal segments (PS/DS boundary). CDKL-1 appears to function independently from several factors that influence cilium length, namely the kinases DYF-5 (mammalian CILK1/MAK) and NEKL-1 (NEK9), as well as the depolymerizing kinesins KLP-13 (KIF19) and KLP-7 (KIF2). However, a different kinase, DYF-18 (CCRK), is needed for the correct localization and function of CDKL-1 and similarly influences the length of the proximal segment. Loss of CDKL-1, which affects proximal segment length without impairing overall ciliary microtubule structural integrity, also impairs cilium-dependent processes, namely cGMP-signaling-dependent body length control and CO2avoidance. Collectively, our findings suggest that cilium length is regulated by various pathways and that the IFT-associated kinase CDKL-1 is essential for the construction of a specific ciliary compartment and contributes to development and sensory physiology.