scholarly journals SWR1-independent association of H2A.Z to the LINC complex promotes meiotic chromosome motion

2020 ◽  
Author(s):  
Sara González-Arranz ◽  
Jennifer M. Gardner ◽  
Zulin Yu ◽  
Neem J. Patel ◽  
Jonna Heldrich ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Meiotic Prophase ◽  
Meiotic Chromosome ◽  
Nuclear Periphery ◽  
The Sun ◽  
Chromosome Movement ◽  
Linc Complex ◽  
Associated Factor ◽  
Independent Association ◽  
Chromosome Motion

ABSTRACTThe H2A.Z histone variant is deposited into chromatin by the SWR1 complex affecting multiple aspects of meiosis. Here we describe a SWR1-independent localization of H2A.Z at meiotic telomeres and the centrosome. We demonstrate that H2A.Z colocalizes and interacts with Mps3, the SUN component of the LINC complex that spans the nuclear envelope and links meiotic telomeres to the cytoskeleton promoting meiotic chromosome movement. H2A.Z also interacts with the meiosis-specific Ndj1 protein that anchors telomeres to the nuclear periphery via Mps3. Telomeric localization of H2A.Z depends on Ndj1 and the N-terminal domain of Mps3. Although telomeric attachment to the nuclear envelope is maintained in the absence of H2A.Z, the distribution of Mps3 is altered. The velocity of chromosome movement during meiotic prophase I is reduced in the htz1Δ mutant lacking H2A.Z, but it is unaffected in swr1Δ cells. We reveal that H2A.Z is an additional LINC-associated factor that contributes to promote telomere-driven chromosome motion critical for error-free gametogenesis.

scholarly journals SWR1-Independent Association of H2A.Z to the LINC Complex Promotes Meiotic Chromosome Motion

2020 ◽  
Vol 8 ◽  
Author(s):  
Sara González-Arranz ◽  
Jennifer M. Gardner ◽  
Zulin Yu ◽  
Neem J. Patel ◽  
Jonna Heldrich ◽  
...  
Keyword(s):  
Meiotic Chromosome ◽  
Linc Complex ◽  
Independent Association ◽  
Chromosome Motion

scholarly journals A molecular mechanism for LINC complex branching by structurally diverse SUN-KASH 6:6 assemblies

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Manickam Gurusaran ◽  
Owen Richard Davies
Keyword(s):  
Nuclear Envelope ◽  
Molecular Mechanism ◽  
Complex Network ◽  
Meiotic Chromosome ◽  
Force Distribution ◽  
The Sun ◽  
Linc Complex ◽  
Cellular Functions ◽  
Zinc Coordination ◽  
Chromosome Movements

The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex mechanically couples cytoskeletal and nuclear components across the nuclear envelope to fulfil a myriad of cellular functions, including nuclear shape and positioning, hearing, and meiotic chromosome movements. The canonical model is that 3:3 interactions between SUN and KASH proteins underlie the nucleocytoskeletal linkages provided by the LINC complex. Here, we provide crystallographic and biophysical evidence that SUN-KASH is a constitutive 6:6 complex in which two constituent 3:3 complexes interact head-to-head. A common SUN-KASH topology is achieved through structurally diverse 6:6 interaction mechanisms by distinct KASH proteins, including zinc-coordination by Nesprin-4. The SUN-KASH 6:6 interface provides a molecular mechanism for the establishment of integrative and distributive connections between 3:3 structures within a branched LINC complex network. In this model, SUN-KASH 6:6 complexes act as nodes for force distribution and integration between adjacent SUN and KASH molecules, enabling the coordinated transduction of large forces across the nuclear envelope.

scholarly journals A molecular mechanism for LINC complex branching by structurally diverse SUN-KASH 6:6 assemblies

2020 ◽  
Author(s):  
Manickam Gurusaran ◽  
Owen R. Davies
Keyword(s):  
Nuclear Envelope ◽  
Molecular Mechanism ◽  
Meiotic Chromosome ◽  
Current Model ◽  
Force Distribution ◽  
The Sun ◽  
Linc Complex ◽  
Cellular Functions ◽  
Zinc Coordination ◽  
Chromosome Movements

SummaryThe LINC complex mechanically couples cytoskeletal and nuclear components across the nuclear envelope to fulfil a myriad of cellular functions, including nuclear shape and positioning, hearing and meiotic chromosome movements. The canonical model of the LINC complex is of individual linear nucleocytoskeletal linkages provided by 3:3 interactions between SUN and KASH proteins. Here, we provide crystallographic and biophysical evidence that SUN-KASH is a constitutive 6:6 complex in which two SUN trimers interact back-to-back. A common SUN-KASH topology is achieved through structurally diverse 6:6 interaction mechanisms by distinct KASH proteins, including zinc-coordination by Nesprin-4. The SUN-KASH 6:6 complex is incompatible with the current model of a linear LINC complex and instead suggests the formation of a branched LINC complex network. In this model, SUN-KASH 6:6 complexes act as nodes for force distribution and integration between adjacent SUN and KASH molecules, enabling the coordinated transduction of large forces across the nuclear envelope.

scholarly journals Phosphorylation of luminal region of the SUN-domain protein Mps3 promotes nuclear envelope localization during meiosis

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Hanumanthu BD Prasada Rao ◽  
Takeshi Sato ◽  
Kiran Challa ◽  
Yurika Fujita ◽  
Miki Shinohara ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Nuclear Envelope ◽  
Meiotic Chromosome ◽  
Linc Complex ◽  
Dependent Protein ◽  
Domain Protein ◽  
Protein Ensembles ◽  
Chromosome Motion ◽  
Sun Domain ◽  
Luminal Region

During meiosis, protein ensembles in the nuclear envelope (NE) containing SUN- and KASH-domain proteins, called linker nucleocytoskeleton and cytoskeleton (LINC) complex, promote the chromosome motion. Yeast SUN-domain protein, Mps3, forms multiple meiosis-specific ensembles on NE, which show dynamic localisation for chromosome motion; however, the mechanism by which these Mps3 ensembles are formed during meiosis remains largely unknown. Here, we showed that the cyclin-dependent protein kinase (CDK) and Dbf4-dependent Cdc7 protein kinase (DDK) regulate meiosis-specific dynamics of Mps3 on NE, particularly by mediating the resolution of Mps3 clusters and telomere clustering. We also found that the luminal region of Mps3 juxtaposed to the inner nuclear membrane is required for meiosis-specific localisation of Mps3 on NE. Negative charges introduced by meiosis-specific phosphorylation in the luminal region of Mps3 alter its interaction with negatively charged lipids by electric repulsion in reconstituted liposomes. Phospho-mimetic substitution in the luminal region suppresses the localisation of Mps3 via the inactivation of CDK or DDK. Our study revealed multi-layered phosphorylation-dependent regulation of the localisation of Mps3 on NE for meiotic chromosome motion and NE remodelling.

scholarly journals Regulating chromosomal movement by the cochaperone FKB-6 ensures timely pairing and synapsis

2017 ◽  
Vol 216 (2) ◽  
pp. 393-408 ◽  
Author(s):  
Benjamin Alleva ◽  
Nathan Balukoff ◽  
Amy Peiper ◽  
Sarit Smolikove
Keyword(s):  
Nuclear Envelope ◽  
Chromosome Pairing ◽  
Meiotic Prophase ◽  
Homologous Chromosome ◽  
Strand Break ◽  
Crossing Over ◽  
Chromosome Movement ◽  
Microtubule Network ◽  
Homologous Chromosome Pairing ◽  
Proper Movement

In meiotic prophase I, homologous chromosome pairing is promoted through chromosome movement mediated by nuclear envelope proteins, microtubules, and dynein. After proper homologue pairing has been established, the synaptonemal complex (SC) assembles along the paired homologues, stabilizing their interaction and allowing for crossing over to occur. Previous studies have shown that perturbing chromosome movement leads to pairing defects and SC polycomplex formation. We show that FKB-6 plays a role in SC assembly and is required for timely pairing and proper double-strand break repair kinetics. FKB-6 localizes outside the nucleus, and in its absence, the microtubule network is altered. FKB-6 is required for proper movement of dynein, increasing resting time between movements. Attenuating chromosomal movement in fkb-6 mutants partially restores the defects in synapsis, in agreement with FKB-6 acting by decreasing chromosomal movement. Therefore, we suggest that FKB-6 plays a role in regulating dynein movement by preventing excess chromosome movement, which is essential for proper SC assembly and homologous chromosome pairing.

scholarly journals Identification of a meiosis-specific chromosome movement pattern induced by persistent DNA damage

2020 ◽  
Author(s):  
Daniel León-Periñán ◽  
Alfonso Fernández-Álvarez
Keyword(s):  
Dna Damage ◽  
Meiotic Prophase ◽  
Meiotic Chromosome ◽  
Three Dimensional ◽  
Model Organism ◽  
Movement Pattern ◽  
Time Lapse ◽  
Chromosome Movement ◽  
Nuclear Movement ◽  
Chromosome Associations

ABSTRACTAs one of the main events occurring during meiotic prophase, the dynamics of meiotic chromosome movement is not yet well understood. Currently, although it is well-established that chromosome movement takes an important role during meiotic recombination promoting the pairing between homologous chromosomes and avoiding excessive chromosome associations, it is mostly unclear whether those movements follow a particular fixed pattern, or are stochastically distributed. Using Schizosaccharomyces pombe as a model organism, which exhibits dramatic meiotic nuclear oscillations, we have developed a computationally automatized statistical analysis of three-dimensional time-lapse fluorescence information in order to characterize nuclear trajectories and morphological patterns during meiotic prophase. This approach allowed us to identify a patterned oscillatory microvariation during the meiotic nuclear motion. Additionally, we showed evidence suggesting that this unexpected oscillatory motif might be due to the detection of persistent DNA damage during the nuclear movement, supporting how the nucleus also regulates its oscillations. Our computationally automatized tool will be useful for the identification of new patterns of nuclear oscillations during gametogenesis.

scholarly journals Architecture of the Nuclear Periphery of Rat Pachytene Spermatocytes: Distribution of Nuclear Envelope Proteins in Relation to Synaptonemal Complex Attachment Sites

1999 ◽  
Vol 10 (4) ◽  
pp. 1235-1245 ◽  
Author(s):  
Manfred Alsheimer ◽  
Elisabeth von Glasenapp ◽  
Robert Hock ◽  
Ricardo Benavente
Keyword(s):  
Nuclear Envelope ◽  
Synaptonemal Complex ◽  
Meiotic Prophase ◽  
Nuclear Periphery ◽  
Cell Fractionation ◽  
Nuclear Interior ◽  
Meiotic Chromosomes ◽  
Attachment Sites ◽  
Form Part ◽  
Pachytene Spermatocytes

The nucleus of spermatocytes provides during the first meiotic prophase an interesting model for investigating relationships of the nuclear envelope (NE) with components of the nuclear interior. During the pachytene stage, meiotic chromosomes are synapsed via synaptonemal complexes (SCs) and attached through both ends to the nuclear periphery. This association is dynamic because chromosomes move during the process of synapsis and desynapsis that takes place during meiotic prophase. The NE of spermatocytes possesses some peculiarities (e.g., lower stability than in somatic cells, expression of short meiosis-specific lamin isoforms called C2 and B3) that could be critically involved in this process. For better understanding of the association of chromosomes with the nuclear periphery, in the present study we have investigated the distribution of NE proteins in relation to SC attachment sites. A major outcome was the finding that lamin C2 is distributed in the form of discontinuous domains at the NE of spermatocytes and that SC attachment sites are embedded in these domains. Lamin C2 appears to form part of larger structures as suggested by cell fractionation experiments. According to these results, we propose that the C2-containing domains represent local reinforcements of the NE that are involved in the proper attachment of SCs.

scholarly journals Samp1 Mislocalization in Emery-Dreifuss Muscular Dystrophy

Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 170 ◽  
Author(s):  
Elisabetta Mattioli ◽  
Marta Columbaro ◽  
Mohammed Hakim Jafferali ◽  
Elisa Schena ◽  
Einar Hallberg ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Membrane Protein ◽  
Nuclear Envelope ◽  
Muscle Cell ◽  
Nuclear Periphery ◽  
Linc Complex ◽  
Cell Nuclei ◽  
Nuclear Movement ◽  
Prelamin A ◽  
Human Myotubes

LMNA linked-Emery-Dreifuss muscular dystrophy (EDMD2) is a rare disease characterized by muscle weakness, muscle wasting, and cardiomyopathy with conduction defects. The mutated protein lamin A/C binds several nuclear envelope components including the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex and the inner nuclear membrane protein Samp1 (Spindle Associated Membrane Protein 1). Considering that Samp1 is upregulated during muscle cell differentiation and it is involved in nuclear movement, we hypothesized that it could be part of the protein platform formed by LINC proteins and prelamin A at the myotube nuclear envelope and, as previously demonstrated for those proteins, could be affected in EDMD2. Our results show that Samp1 is uniformly distributed at the nuclear periphery of normal human myotubes and committed myoblasts, but its anchorage at the nuclear poles is related to the presence of farnesylated prelamin A and it is disrupted by the loss of prelamin A farnesylation. Moreover, Samp1 is absent from the nuclear poles in EDMD2 myotubes, which shows that LMNA mutations associated with muscular dystrophy, due to reduced prelamin A levels in muscle cell nuclei, impair Samp1 anchorage. Conversely, SUN1 pathogenetic mutations do not alter Samp1 localization in myotubes, which suggests that Samp1 lies upstream of SUN1 in nuclear envelope protein complexes. The hypothesis that Samp1 is part of the protein platform that regulates microtubule nucleation from the myotube nuclear envelope in concert with pericentrin and LINC components warrants future investigation. As a whole, our data identify Samp1 as a new contributor to EDMD2 pathogenesis and our data are relevant to the understanding of nuclear clustering occurring in laminopathic muscle.

scholarly journals Maize (Zea mays L.) Nucleoskeletal Proteins Regulate Nuclear Envelope Remodeling and Function in Stomatal Complex Development and Pollen Viability

2021 ◽  
Vol 12 ◽  
Author(s):  
Joseph F. McKenna ◽  
Hardeep K. Gumber ◽  
Zachary M. Turpin ◽  
Alexis M. Jalovec ◽  
Andre C. Kartick ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Zea Mays L ◽  
Fluorescent Protein ◽  
Pollen Viability ◽  
Nuclear Periphery ◽  
Nuclear Architecture ◽  
Linc Complex ◽  
Stomatal Complex ◽  
Complex Development ◽  
And Function

In eukaryotes, the nuclear envelope (NE) encloses chromatin and separates it from the rest of the cell. The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex physically bridges across the NE, linking nuclear and cytoplasmic components. In plants, these LINC complexes are beginning to be ascribed roles in cellular and nuclear functions, including chromatin organization, regulation of nuclei shape and movement, and cell division. Homologs of core LINC components, KASH and SUN proteins, have previously been identified in maize. Here, we characterized the presumed LINC-associated maize nucleoskeletal proteins NCH1 and NCH2, homologous to members of the plant NMCP/CRWN family, and MKAKU41, homologous to AtKAKU4. All three proteins localized to the nuclear periphery when transiently and heterologously expressed as fluorescent protein fusions in Nicotiana benthamiana. Overexpression of MKAKU41 caused dramatic changes in the organization of the nuclear periphery, including nuclear invaginations that stained positive for non-nucleoplasmic markers of the inner and outer NE membranes, and the ER. The severity of these invaginations was altered by changes in LINC connections and the actin cytoskeleton. In maize, MKAKU41 appeared to share genetic functions with other LINC components, including control of nuclei shape, stomatal complex development, and pollen viability. Overall, our data show that NCH1, NCH2, and MKAKU41 have characteristic properties of LINC-associated plant nucleoskeletal proteins, including interactions with NE components suggestive of functions at the nuclear periphery that impact the overall nuclear architecture.

scholarly journals The Caenorhabditis elegans SUN protein UNC-84 interacts with lamin to transfer forces from the cytoplasm to the nucleoskeleton during nuclear migration

2014 ◽  
Vol 25 (18) ◽  
pp. 2853-2865 ◽  
Author(s):  
Courtney R. Bone ◽  
Erin C. Tapley ◽  
Mátyás Gorjánácz ◽  
Daniel A. Starr
Keyword(s):  
Caenorhabditis Elegans ◽  
Nuclear Envelope ◽  
Missense Mutation ◽  
Nuclear Membrane ◽  
Nuclear Migration ◽  
Live Imaging ◽  
Mechanical Forces ◽  
The Sun ◽  
Critical Component ◽  
Linc Complex

Nuclear migration is a critical component of many cellular and developmental processes. The nuclear envelope forms a barrier between the cytoplasm, where mechanical forces are generated, and the nucleoskeleton. The LINC complex consists of KASH proteins in the outer nuclear membrane and SUN proteins in the inner nuclear membrane that bridge the nuclear envelope. How forces are transferred from the LINC complex to the nucleoskeleton is poorly understood. The Caenorhabditis elegans lamin, LMN-1, is required for nuclear migration and interacts with the nucleoplasmic domain of the SUN protein UNC-84. This interaction is weakened by the unc-84(P91S) missense mutation. These mutant nuclei have an intermediate nuclear migration defect—live imaging of nuclei or LMN-1::GFP shows that many nuclei migrate normally, others initiate migration before subsequently failing, and others fail to begin migration. At least one other component of the nucleoskeleton, the NET5/Samp1/Ima1 homologue SAMP-1, plays a role in nuclear migration. We propose a nut-and-bolt model to explain how forces are dissipated across the nuclear envelope during nuclear migration. In this model, SUN/KASH bridges serve as bolts through the nuclear envelope, and nucleoskeleton components LMN-1 and SAMP-1 act as both nuts and washers on the inside of the nucleus.

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