Senatore Emanuela, Iannucci Rosa, Chiuso Francesco, Delle Donne Rossella, Rinaldi Laura, Feliciello Antonio
Department of Molecular Medicine and Medical Biotechnology, University Federico II, Naples, Italy.
Front Cell Dev Biol. 2022 May 11;10:833086. doi: 10.3389/fcell.2022.833086. eCollection 2022.
Primary cilia are microtubule-based, non-motile sensory organelles present in most types of growth-arrested eukaryotic cells. They are transduction hubs that receive and transmit external signals to the cells in order to control growth, differentiation and development. Mutations of genes involved in the formation, maintenance or disassembly of ciliary structures cause a wide array of developmental genetic disorders, also known as ciliopathies. The primary cilium is formed during G1 in the cell cycle and disassembles at the G2/M transition. Following the completion of the cell division, the cilium reassembles in G1. This cycle is finely regulated at multiple levels. The ubiquitin-proteasome system (UPS) and the autophagy machinery, two main protein degradative systems in cells, play a fundamental role in cilium dynamics. Evidence indicate that UPS, autophagy and signaling pathways may act in synergy to control the ciliary homeostasis. However, the mechanisms involved and the links between these regulatory systems and cilium biogenesis, dynamics and signaling are not well defined yet. Here, we discuss the reciprocal regulation of signaling pathways and proteolytic machineries in the control of the assembly and disassembly of the primary cilium, and the impact of the derangement of these regulatory networks in human ciliopathies.
初级纤毛是基于微管的非运动性感觉细胞器，存在于大多数类型的生长停滞的真核细胞中。它们是转导枢纽，接收并向细胞传递外部信号，以控制生长、分化和发育。参与纤毛结构形成、维持或拆卸的基因突变会导致多种发育性遗传疾病，也称为纤毛病。初级纤毛在细胞周期的G1期形成，并在G2/M转换时解体。细胞分裂完成后，纤毛在G1期重新组装。这个循环在多个层面受到精细调节。泛素-蛋白酶体系统（UPS）和自噬机制是细胞中的两个主要蛋白质降解系统，在纤毛动态变化中起基本作用。有证据表明，UPS、自噬和信号通路可能协同作用以控制纤毛稳态。然而，其中涉及的机制以及这些调节系统与纤毛生物发生、动态变化和信号传导之间的联系尚未明确界定。在这里，我们讨论信号通路和蛋白水解机制在控制初级纤毛组装和解体中的相互调节，以及这些调节网络紊乱对人类纤毛病的影响。
