MKS-NPHP module proteins control ciliary shedding at the transition zone
MKS-NPHP module proteins control ciliary shedding at the transition zone
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DOI：
10.1371/journal.pbio.3000640
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发表时间：
2020-03-01
期刊：
影响因子：
9.8
通讯作者：
Tassin, Anne-Marie
中科院分区：
文献类型：
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作者：
Gogendeau, Delphine;Lemullois, Michel;Tassin, Anne-Marie
从单细胞生物到后生动物都会发生纤毛脱落。尽管在细胞周期和神经发生过程中是必需的，但这个过程仍然知之甚少。在所有的细胞模型中，这种现象发生在过渡区(TZ)的远端，这表明了保守的分子机制。TZ模块蛋白(Meckel Gruber综合征[MKS]/肾单位[NPHP]/290 kDa中心体蛋白[CEP290]/视网膜色素变性GTP酶调节因子相互作用蛋白1[RPGRIP1L])与TZ的形成和功能密切相关。为了确定它们是否控制蜕皮，我们研究了其中5个基因(跨膜蛋白107[TMEM107]、跨膜蛋白216[TMEM216]、CEP290、RPGRIP1L和NPHP4)在草履虫中的功能。所有蛋白质都被招募到生长中的纤毛的TZ，并以9倍对称的方式定位在TZ最远端的水平。我们证明了MKS2/TMEM216和TMEM107蛋白的缺失会导致一些纤毛的持续降解，而NPHP4、CEP290或RPGRIP1L的缺失则会阻止钙离子/乙醇的降解。我们的结果首次证明了保守的TZ蛋白在纤毛运动中的作用，并为理解运动纤毛生理学开辟了新的方向。
Ciliary shedding occurs from unicellular organisms to metazoans. Although required during the cell cycle and during neurogenesis, the process remains poorly understood. In all cellular models, this phenomenon occurs distal to the transition zone (TZ), suggesting conserved molecular mechanisms. The TZ module proteins (Meckel Gruber syndrome [MKS]/Nephronophtysis [NPHP]/Centrosomal protein of 290 kDa [CEP290]/Retinitis pigmentosa GTPase regulator-Interacting Protein 1-Like Protein [RPGRIP1L]) are known to cooperate to establish TZ formation and function. To determine whether they control deciliation, we studied the function of 5 of them (Transmembrane protein 107 [TMEM107], Transmembrane protein 216 [TMEM216], CEP290, RPGRIP1L, and NPHP4) in Paramecium. All proteins are recruited to the TZ of growing cilia and localize with 9-fold symmetry at the level of the most distal part of the TZ. We demonstrate that depletion of the MKS2/TMEM216 and TMEM107 proteins induces constant deciliation of some cilia, while depletion of either NPHP4, CEP290, or RPGRIP1L prevents Ca2+/EtOH deciliation. Our results constitute the first evidence for a role of conserved TZ proteins in deciliation and open new directions for understanding motile cilia physiology.