Agote-Arán Arantxa, Lin Junyan, Sumara Izabela
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France.
Centre National de la Recherche Scientifique UMR 7104, Strasbourg, France.
Front Cell Dev Biol. 2021 Dec 16;9:755847. doi: 10.3389/fcell.2021.755847. eCollection 2021.
Nuclear pore complexes (NPCs) are embedded in the nuclear envelope (NE) where they ensure the transport of macromolecules between the nucleus and the cytoplasm. NPCs are built from nucleoporins (Nups) through a sequential assembly order taking place at two different stages during the cell cycle of mammalian cells: at the end of mitosis and during interphase. In addition, fragile X-related proteins (FXRPs) can interact with several cytoplasmic Nups and facilitate their localization to the NE during interphase likely through a microtubule-dependent mechanism. In the absence of FXRPs or microtubule-based transport, Nups aberrantly localize to the cytoplasm forming the so-called cytoplasmic nucleoporin granules (CNGs), compromising NPCs' function on protein export. However, it remains unknown if Nup synthesis or degradation mechanisms are linked to the FXRP-Nup pathway and if and how the action of FXRPs on Nups is coordinated with the cell cycle progression. Here, we show that Nup localization defects observed in the absence of FXR1 are independent of active protein translation. CNGs are cleared in an autophagy- and proteasome-independent manner, and their presence is restricted to the early G1 phase of the cell cycle. Our results thus suggest that a pool of cytoplasmic Nups exists that contributes to the NPC assembly specifically during early G1 to ensure NPC homeostasis at a short transition from mitosis to the onset of interphase.
核孔复合体（NPCs）嵌入核膜（NE）中，在那里它们确保大分子在细胞核与细胞质之间的运输。NPCs由核孔蛋白（Nups）通过在哺乳动物细胞周期的两个不同阶段发生的顺序组装顺序构建而成：在有丝分裂末期和间期。此外，脆性X相关蛋白（FXRPs）可以与几种细胞质Nups相互作用，并可能通过微管依赖机制促进它们在间期定位于NE。在没有FXRPs或基于微管的运输的情况下，Nups异常定位于细胞质中，形成所谓的细胞质核孔蛋白颗粒（CNGs），损害NPCs在蛋白质输出方面的功能。然而，Nup合成或降解机制是否与FXRP-Nup途径相关，以及FXRPs对Nups的作用是否以及如何与细胞周期进程协调，仍然未知。在这里，我们表明在没有FXR1的情况下观察到的Nup定位缺陷与活性蛋白质翻译无关。CNGs以自噬和蛋白酶体非依赖的方式清除，并且它们的存在仅限于细胞周期的早期G1期。因此，我们的结果表明存在一群细胞质Nups，它们在早期G1期间专门促进NPC组装，以确保在从有丝分裂到间期开始的短暂过渡期间NPC的稳态。
