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NudCL2 is an autophagy receptor that mediates selective autophagic degradation of CP110 at mother centrioles to promote ciliogenesis
Cell Research ( IF 44.1 ) Pub Date : 2021-09-03 , DOI: 10.1038/s41422-021-00560-3
Min Liu 1, 2 , Wen Zhang 2, 3 , Min Li 2 , Jiaxing Feng 2 , Wenjun Kuang 2 , Xiying Chen 2 , Feng Yang 2 , Qiang Sun 2 , Zhangqi Xu 2 , Jianfeng Hua 2 , Chunxia Yang 2 , Wei Liu 2 , Qiang Shu 1 , Yuehong Yang 2 , Tianhua Zhou 2, 3, 4, 5 , Shanshan Xie 1
Affiliation  

Primary cilia extending from mother centrioles are essential for vertebrate development and homeostasis maintenance. Centriolar coiled-coil protein 110 (CP110) has been reported to suppress ciliogenesis initiation by capping the distal ends of mother centrioles. However, the mechanism underlying the specific degradation of mother centriole-capping CP110 to promote cilia initiation remains unknown. Here, we find that autophagy is crucial for CP110 degradation at mother centrioles after serum starvation in MEF cells. We further identify NudC-like protein 2 (NudCL2) as a novel selective autophagy receptor at mother centrioles, which contains an LC3-interacting region (LIR) motif mediating the association of CP110 and the autophagosome marker LC3. Knockout of NudCL2 induces defects in the removal of CP110 from mother centrioles and ciliogenesis, which are rescued by wild-type NudCL2 but not its LIR motif mutant. Knockdown of CP110 significantly attenuates ciliogenesis defects in NudCL2-deficient cells. In addition, NudCL2 morphants exhibit ciliation-related phenotypes in zebrafish, which are reversed by wild-type NudCL2, but not its LIR motif mutant. Importantly, CP110 depletion significantly reverses these ciliary phenotypes in NudCL2 morphants. Taken together, our data suggest that NudCL2 functions as an autophagy receptor mediating the selective degradation of mother centriole-capping CP110 to promote ciliogenesis, which is indispensable for embryo development in vertebrates.



中文翻译:

NudCL2 是一种自噬受体,可介导 CP110 在母体中心粒处选择性自噬降解以促进纤毛发生

从母体中心粒延伸的初级纤毛对于脊椎动物发育和体内平衡维持至关重要。据报道,中心粒卷曲螺旋蛋白 110 (CP110) 通过覆盖母中心粒的远端来抑制纤毛发生的起始。然而,母亲中心粒加帽CP110特异性降解促进纤毛起始的机制仍然未知。在这里,我们发现自噬对于 MEF 细胞血清饥饿后母体中心粒的 CP110 降解至关重要。我们进一步将 NudC 样蛋白 2 (NudCL2) 鉴定为母中心粒的新型选择性自噬受体,其包含介导 CP110 和自噬体标志物 LC3 关联的 LC3 相互作用区 (LIR) 基序。NudCL2的淘汰赛诱导从母体中心粒和纤毛发生中去除 CP110 的缺陷,这些缺陷被野生型 NudCL2 但不是其 LIR 基序突变体拯救。敲除CP110可显着减轻 NudCL2 缺陷细胞的纤毛发生缺陷。此外,NudCL2 morphants 在斑马鱼中表现出纤毛相关的表型,这被野生型 NudCL2 逆转,但不是其 LIR 基序突变体。重要的是,CP110耗竭显着逆转了NudCL2 morphants中的这些纤毛表型。总之,我们的数据表明,NudCL2 作为一种自噬受体发挥作用,介导母体中心粒封端 CP110 的选择性降解以促进纤毛发生,这对于脊椎动物的胚胎发育是必不可少的。

更新日期:2021-09-03
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