scholarly journals Essential Roles for Caenorhabditis elegans Lamin Gene in Nuclear Organization, Cell Cycle Progression, and Spatial Organization of Nuclear Pore Complexes

2000 ◽  
Vol 11 (11) ◽  
pp. 3937-3947 ◽  
Author(s):  
Jun Liu ◽  
Tom Rolef Ben-Shahar ◽  
Dieter Riemer ◽  
Millet Treinin ◽  
Perah Spann ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Caenorhabditis Elegans ◽  
Cell Cycle Progression ◽  
Spatial Organization ◽  
Nuclear Periphery ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Cycle Progression ◽  
Nuclear Lamins ◽  
Pore Complexes

Caenorhabditis elegans has a single lamin gene, designated lmn-1 (previously termed CeLam-1). Antibodies raised against the lmn-1 product (Ce-lamin) detected a 64-kDa nuclear envelope protein. Ce-lamin was detected in the nuclear periphery of all cells except sperm and was found in the nuclear interior in embryonic cells and in a fraction of adult cells. Reductions in the amount of Ce-lamin protein produce embryonic lethality. Although the majority of affected embryos survive to produce several hundred nuclei, defects can be detected as early as the first nuclear divisions. Abnormalities include rapid changes in nuclear morphology during interphase, loss of chromosomes, unequal separation of chromosomes into daughter nuclei, abnormal condensation of chromatin, an increase in DNA content, and abnormal distribution of nuclear pore complexes (NPCs). Under conditions of incomplete RNA interference, a fraction of embryos escaped embryonic arrest and continue to develop through larval life. These animals exhibit additional phenotypes including sterility and defective segregation of chromosomes in germ cells. Our observations show thatlmn-1 is an essential gene in C. elegans, and that the nuclear lamins are involved in chromatin organization, cell cycle progression, chromosome segregation, and correct spacing of NPCs.

scholarly journals Spatial control of nucleoporin assembly by Fragile X-related proteins

2019 ◽  
Author(s):  
Arantxa Agote-Arán ◽  
Stephane Schmucker ◽  
Katerina Jerabkova ◽  
Inès Jmel Boyer ◽  
Alessandro Berto ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Nuclear Envelope ◽  
Fragile X Syndrome ◽  
Cell Cycle Progression ◽  
Fragile X ◽  
Nuclear Pore ◽  
Nuclear Morphology ◽  
Nuclear Pore Complexes ◽  
Cycle Progression ◽  
Pore Complexes

SummaryNucleoporins (Nups) build highly organized Nuclear Pore Complexes (NPCs) at the nuclear envelope (NE). Several Nups assemble into a sieve-like hydrogel within the central channel of the NPCs to regulate nucleocytoplasmic exchange. In the cytoplasm, a large excess of soluble Nups has been reported, but how their assembly is restricted to the NE is currently unknown. Here we show that Fragile X-related protein 1 (FXR1) can interact with several Nups and facilitate their localization to the NE during interphase through a microtubule and dynein-dependent mechanism. Downregulation of FXR1 or closely related orthologs FXR2 and Fragile X mental retardation protein (FMRP) leads to the accumulation of cytoplasmic Nup protein condensates. Likewise, several models of Fragile X syndrome (FXS), characterized by a loss of FMRP, also accumulate cytoplasmic Nup aggregates. These aggregate-containing cells display aberrant nuclear morphology and a delay in G1 cell cycle progression. Our results reveal an unexpected role for the FXR protein family and dynein in the spatial regulation of nucleoporin assembly.HighlightsCytoplasmic nucleoporins are assembled by Fragile X-related (FXR) proteins and dyneinFXR-Dynein pathway downregulation induces aberrant cytoplasmic aggregation of nucleoporinsCellular models of Fragile X syndrome accumulate aberrant cytoplasmic nucleoporin aggregates.FXR-Dynein pathway regulates nuclear morphology and G1 cell cycle progressioneTOC BlurbNucleoporins (Nups) form Nuclear Pore Complexes (NPCs) at the nuclear envelope. Agote-Arán at al. show how cells inhibit aberrant assembly of Nups in the cytoplasm and identify Fragile X-related (FXR) proteins and dynein that facilitate localization of Nups to the nuclear envelope and control G1 cell cycle progression.Graphical abstract

scholarly journals Mps1-mediated release of Mad1 from nuclear pores ensures the fidelity of chromosome segregation

2020 ◽  
Vol 219 (3) ◽  
Author(s):  
Sofia Cunha-Silva ◽  
Mariana Osswald ◽  
Jana Goemann ◽  
João Barbosa ◽  
Luis M. Santos ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Genome Stability ◽  
Cell Cycle Progression ◽  
Spindle Assembly Checkpoint ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Cycle Progression ◽  
Pore Complexes ◽  
Drosophila Cells

The spindle assembly checkpoint (SAC) relies on the recruitment of Mad1-C-Mad2 to unattached kinetochores but also on its binding to Megator/Tpr at nuclear pore complexes (NPCs) during interphase. However, the molecular underpinnings controlling the spatiotemporal redistribution of Mad1-C-Mad2 as cells progress into mitosis remain elusive. Here, we show that activation of Mps1 during prophase triggers Mad1 release from NPCs and that this is required for kinetochore localization of Mad1-C-Mad2 and robust SAC signaling. We find that Mps1 phosphorylates Megator/Tpr to reduce its interaction with Mad1 in vitro and in Drosophila cells. Importantly, preventing Mad1 from binding to Megator/Tpr restores Mad1 accumulation at kinetochores, the fidelity of chromosome segregation, and genome stability in larval neuroblasts of mps1-null mutants. Our findings demonstrate that the subcellular localization of Mad1 is tightly coordinated with cell cycle progression by kinetochore-extrinsic activity of Mps1. This ensures that both NPCs in interphase and kinetochores in mitosis can generate anaphase inhibitors to efficiently preserve genomic stability.

scholarly journals Mps1 releases Mad1 from nuclear pores to ensure a robust mitotic checkpoint and accurate chromosome segregation

2019 ◽  
Author(s):  
Mariana Osswald ◽  
Sofia Cunha-Silva ◽  
Jana Goemann ◽  
João Barbosa ◽  
Luis M Santos ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Cell Cycle Progression ◽  
Spindle Assembly Checkpoint ◽  
Mitotic Checkpoint ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Cycle Progression ◽  
Checkpoint Response ◽  
Pore Complexes

ABSTRACTThe strength of the Spindle Assembly Checkpoint (SAC) depends on the amount of the Mad1-C-Mad2 heterotetramer at kinetochores but also on its binding to Megator/Tpr at nuclear pore complexes (NPCs) during interphase. However, the molecular underpinnings controlling the spatiotemporal redistribution of Mad1-C-Mad2 as cells progress into mitosis remain elusive. Here, we show that Mps1-mediated phosphorylation of Megator/Tpr abolishes its interaction with Mad1 in vitro and in Drosophila cells. Timely activation of Mps1 during prophase triggers Mad1 release from NPCs, which we find to be required for competent kinetochore recruitment of Mad1-C-Mad2 and robust checkpoint response. Importantly, preventing Mad1 binding to Megator/Tpr rescues the fidelity of chromosome segregation and aneuploidy in larval neuroblasts of Drosophila mps1-null mutants. Our findings demonstrate that the subcellular localization of Mad1 is stringently coordinated with cell cycle progression by kinetochore-extrinsic activity of Mps1. This ensures that both NPCs in interphase and kinetochores in mitosis can generate anaphase inhibitors to efficiently preserve genomic stability.

scholarly journals Erratum: Dynamic SUMO modification regulates mitotic chromosome assembly and cell cycle progression in Caenorhabditis elegans

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Federico Pelisch ◽  
Remi Sonneville ◽  
Ehsan Pourkarimi ◽  
Ana Agostinho ◽  
J. Julian Blow ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Caenorhabditis Elegans ◽  
Cell Cycle Progression ◽  
Mitotic Chromosome ◽  
Cycle Progression ◽  
Sumo Modification

Involvement of caveolin-1 in meiotic cell-cycle progression in Caenorhabditis elegans

10.1038/10100 ◽  
1999 ◽  
Vol 1 (2) ◽  
pp. 127-129 ◽  
Author(s):  
Jochen Scheel ◽  
Jagan Srinivasan ◽  
Ulrike Honnert ◽  
Annemarie Henske ◽  
Teymuras V. Kurzchalia
Keyword(s):  
Cell Cycle ◽  
Caenorhabditis Elegans ◽  
Cell Cycle Progression ◽  
Meiotic Cell ◽  
Cycle Progression ◽  
Caveolin 1

scholarly journals Phosphorylation-dependent mitotic SUMOylation drives nuclear envelope–chromatin interactions

2021 ◽  
Vol 220 (12) ◽  
Author(s):  
Christopher Ptak ◽  
Natasha O. Saik ◽  
Ashwini Premashankar ◽  
Diego L. Lapetina ◽  
John D. Aitchison ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nuclear Envelope ◽  
Spatial Organization ◽  
G1 Phase ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Chromatin Binding ◽  
Chromatin Interactions ◽  
Sumo Ligase ◽  
Pore Complexes

In eukaryotes, chromatin binding to the inner nuclear membrane (INM) and nuclear pore complexes (NPCs) contributes to spatial organization of the genome and epigenetic programs important for gene expression. In mitosis, chromatin–nuclear envelope (NE) interactions are lost and then formed again as sister chromosomes segregate to postmitotic nuclei. Investigating these processes in S. cerevisiae, we identified temporally and spatially controlled phosphorylation-dependent SUMOylation events that positively regulate postmetaphase chromatin association with the NE. Our work establishes a phosphorylation-mediated targeting mechanism of the SUMO ligase Siz2 to the INM during mitosis, where Siz2 binds to and SUMOylates the VAP protein Scs2. The recruitment of Siz2 through Scs2 is further responsible for a wave of SUMOylation along the INM that supports the assembly and anchorage of subtelomeric chromatin at the INM and localization of an active gene (INO1) to NPCs during the later stages of mitosis and into G1-phase.

scholarly journals Dynamic SUMO modification regulates mitotic chromosome assembly and cell cycle progression in Caenorhabditis elegans

2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Federico Pelisch ◽  
Remi Sonneville ◽  
Ehsan Pourkarimi ◽  
Ana Agostinho ◽  
J. Julian Blow ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Caenorhabditis Elegans ◽  
Cell Cycle Progression ◽  
Metaphase Plate ◽  
Gene Encoding ◽  
Cycle Progression ◽  
Sumo Protease ◽  
Sumo Conjugation ◽  
Centromeric Protein ◽  
Cycle Regulation

Abstract The small ubiquitin-like modifier (SUMO), initially characterized as a suppressor of a mutation in the gene encoding the centromeric protein MIF2, is involved in many aspects of cell cycle regulation. The dynamics of conjugation and deconjugation and the role of SUMO during the cell cycle remain unexplored. Here we used Caenorhabditis elegans to establish the contribution of SUMO to a timely and accurate cell division. Chromatin-associated SUMO conjugates increase during metaphase but decrease rapidly during anaphase. Accumulation of SUMO conjugates on the metaphase plate and proper chromosome alignment depend on the SUMO E2 conjugating enzyme UBC-9 and SUMO E3 ligase PIASGEI-17. Deconjugation is achieved by the SUMO protease ULP-4 and is crucial for correct progression through the cell cycle. Moreover, ULP-4 is necessary for Aurora BAIR-2 extraction from chromatin and relocation to the spindle mid-zone. Our results show that dynamic SUMO conjugation plays a role in cell cycle progression.

Sign in / Sign up

Export Citation Format

Share Document