Fragile X–Related Protein 1 Regulates Nucleoporin Localization in a Cell Cycle–Dependent Manner
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 m...
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| Format: | Article |
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.755847/full |
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| author | Arantxa Agote-Arán Arantxa Agote-Arán Arantxa Agote-Arán Arantxa Agote-Arán Junyan Lin Junyan Lin Junyan Lin Junyan Lin Izabela Sumara Izabela Sumara Izabela Sumara Izabela Sumara |
| author_facet | Arantxa Agote-Arán Arantxa Agote-Arán Arantxa Agote-Arán Arantxa Agote-Arán Junyan Lin Junyan Lin Junyan Lin Junyan Lin Izabela Sumara Izabela Sumara Izabela Sumara Izabela Sumara |
| author_sort | Arantxa Agote-Arán |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T21:18:50Z |
| format | Article |
| id | doaj.art-4e92092129944cd8af76119f58f19d80 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-13T21:18:50Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-4e92092129944cd8af76119f58f19d802022-12-21T23:31:10ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-12-01910.3389/fcell.2021.755847755847Fragile X–Related Protein 1 Regulates Nucleoporin Localization in a Cell Cycle–Dependent MannerArantxa Agote-Arán0Arantxa Agote-Arán1Arantxa Agote-Arán2Arantxa Agote-Arán3Junyan Lin4Junyan Lin5Junyan Lin6Junyan Lin7Izabela Sumara8Izabela Sumara9Izabela Sumara10Izabela Sumara11Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, FranceCentre National de la Recherche Scientifique UMR 7104, Strasbourg, FranceInstitut National de la Santé et de la Recherche Médicale U964, Strasbourg, FranceUniversité de Strasbourg, Strasbourg, FranceInstitut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, FranceCentre National de la Recherche Scientifique UMR 7104, Strasbourg, FranceInstitut National de la Santé et de la Recherche Médicale U964, Strasbourg, FranceUniversité de Strasbourg, Strasbourg, FranceInstitut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, FranceCentre National de la Recherche Scientifique UMR 7104, Strasbourg, FranceInstitut National de la Santé et de la Recherche Médicale U964, Strasbourg, FranceUniversité de Strasbourg, Strasbourg, FranceNuclear 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.https://www.frontiersin.org/articles/10.3389/fcell.2021.755847/fullcell cycleG1 phasenucleoporinsnuclear pore complexphase separationFXR1 |
| spellingShingle | Arantxa Agote-Arán Arantxa Agote-Arán Arantxa Agote-Arán Arantxa Agote-Arán Junyan Lin Junyan Lin Junyan Lin Junyan Lin Izabela Sumara Izabela Sumara Izabela Sumara Izabela Sumara Fragile X–Related Protein 1 Regulates Nucleoporin Localization in a Cell Cycle–Dependent Manner Frontiers in Cell and Developmental Biology cell cycle G1 phase nucleoporins nuclear pore complex phase separation FXR1 |
| title | Fragile X–Related Protein 1 Regulates Nucleoporin Localization in a Cell Cycle–Dependent Manner |
| title_full | Fragile X–Related Protein 1 Regulates Nucleoporin Localization in a Cell Cycle–Dependent Manner |
| title_fullStr | Fragile X–Related Protein 1 Regulates Nucleoporin Localization in a Cell Cycle–Dependent Manner |
| title_full_unstemmed | Fragile X–Related Protein 1 Regulates Nucleoporin Localization in a Cell Cycle–Dependent Manner |
| title_short | Fragile X–Related Protein 1 Regulates Nucleoporin Localization in a Cell Cycle–Dependent Manner |
| title_sort | fragile x related protein 1 regulates nucleoporin localization in a cell cycle dependent manner |
| topic | cell cycle G1 phase nucleoporins nuclear pore complex phase separation FXR1 |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.755847/full |
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