scholarly journals Mad1’s ability to interact with Mad2 is essential to regulate and monitor meiotic synapsis in C. elegans

PLoS Genetics ◽  
2021 ◽  
Vol 17 (11) ◽  
pp. e1009598
Author(s):  
Alice Devigne ◽  
Needhi Bhalla
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Periphery ◽  
Spindle Checkpoint ◽  
Primary Role ◽  
Cis Acting ◽  
C Elegans ◽  
Important Regulator ◽  
Meiotic Synapsis ◽  
Segregation Of Chromosomes

Meiotic homolog synapsis is essential to ensure accurate segregation of chromosomes during meiosis. In C. elegans, proper regulation of synapsis and a checkpoint that monitors synapsis relies on the spindle checkpoint components, Mad1 and Mad2, and Pairing Centers (PCs), cis-acting loci that interact with the nuclear envelope to mobilize chromosomes within the nucleus. Here, we test what specific functions of Mad1 and Mad2 are required to regulate and monitor synapsis. We find that a mutation that prevents Mad1’s localization to the nuclear periphery abolishes the synapsis checkpoint but has no effect on Mad2’s localization to the nuclear periphery or synapsis. By contrast, a mutation that prevents Mad1’s interaction with Mad2 abolishes the synapsis checkpoint, delays synapsis and fails to localize Mad2 to the nuclear periphery. These data indicate that Mad1’s primary role in regulating synapsis is through control of Mad2 and that Mad2 can bind other factors at the nuclear periphery. We also tested whether Mad2’s ability to adopt a specific conformation associated with its activity during spindle checkpoint function is required for its role in meiosis. A mutation that prevents Mad2 from adopting its active conformer fails to localize to the nuclear periphery, abolishes the synapsis checkpoint and exhibits substantial defects in meiotic synapsis. Thus, Mad2, and its regulation by Mad1, is an important regulator of meiotic synapsis in C. elegans.

scholarly journals Mad1’s ability to interact with Mad2 is essential to regulate and monitor meiotic synapsis in C. elegans

2021 ◽  
Author(s):  
Alice Devigne ◽  
Needhi Bhalla
Keyword(s):  
Nuclear Envelope ◽  
Meiotic Prophase ◽  
Nuclear Periphery ◽  
Spindle Checkpoint ◽  
Primary Role ◽  
Cis Acting ◽  
C Elegans ◽  
Meiotic Synapsis ◽  
Segregation Of Chromosomes

Meiotic homolog synapsis is essential to ensure accurate segregation of chromosomes during meiosis.  In C. elegans , synapsis and a checkpoint that monitors synapsis relies on the spindle checkpoint components, Mad1 and Mad2, and Pairing Centers (PCs), cis-acting loci that interact with the nuclear envelope to mobilize chromosomes within the nucleus. Here, we show that mutations in some spindle checkpoint mutants affect PC movement early in meiotic prophase, consistent with a link between PC mobility and the regulation of synapsis. Further, we test what specific functions of Mad1 and Mad2 are required to regulate and monitor synapsis. We find that a mutation that abrogates Mad1’s localization to the nuclear periphery abolishes the synapsis checkpoint but has no effect on Mad2’s localization to the nuclear periphery or synapsis. By contrast, a mutation that prevents Mad1’s interaction with Mad2 abolishes the synapsis checkpoint, delays synapsis and fails to localize Mad2 to the nuclear periphery. These data indicate that Mad1’s primary role in regulating synapsis is through control of Mad2 and that Mad2 can bind other factors at the nuclear periphery. We also tested whether Mad2’s ability to adopt a specific conformation associated with its activity during spindle checkpoint function is required for its role in meiosis. A mutation that prevents Mad2 from adopting its active conformer fails to localize to the nuclear periphery, abolishes the synapsis checkpoint and exhibits substantial defects in meiotic synapsis. Thus, Mad2, and its regulation by Mad1, is a major regulator of meiotic synapsis in C. elegans .

scholarly journals Spindle assembly checkpoint proteins regulate and monitor meiotic synapsis in C. elegans

2015 ◽  
Vol 211 (2) ◽  
pp. 233-242 ◽  
Author(s):  
Tisha Bohr ◽  
Christian R. Nelson ◽  
Erin Klee ◽  
Needhi Bhalla
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Meiotic Chromosome ◽  
Spindle Assembly ◽  
Anaphase Promoting Complex ◽  
Checkpoint Response ◽  
Checkpoint Proteins ◽  
Cis Acting ◽  
C Elegans ◽  
Meiotic Synapsis ◽  
The Stability

Homologue synapsis is required for meiotic chromosome segregation, but how synapsis is initiated between chromosomes is poorly understood. In Caenorhabditis elegans, synapsis and a checkpoint that monitors synapsis depend on pairing centers (PCs), cis-acting loci that interact with nuclear envelope proteins, such as SUN-1, to access cytoplasmic microtubules. Here, we report that spindle assembly checkpoint (SAC) components MAD-1, MAD-2, and BUB-3 are required to negatively regulate synapsis and promote the synapsis checkpoint response. Both of these roles are independent of a conserved component of the anaphase-promoting complex, indicating a unique role for these proteins in meiotic prophase. MAD-1 and MAD-2 localize to the periphery of meiotic nuclei and interact with SUN-1, suggesting a role at PCs. Consistent with this idea, MAD-1 and BUB-3 require full PC function to inhibit synapsis. We propose that SAC proteins monitor the stability of pairing, or tension, between homologues to regulate synapsis and elicit a checkpoint response.

A motor independent requirement for Dynein light chain in C. elegans meiotic synapsis

Genetics ◽  
2021 ◽  
Author(s):  
Sara M Fielder ◽  
Tori Kent ◽  
Huiping Ling ◽  
Elizabeth J Gleason ◽  
William G Kelly
Keyword(s):  
Light Chain ◽  
Elevated Temperatures ◽  
Nuclear Periphery ◽  
High Growth ◽  
Binding Motif ◽  
Dynein Light Chain ◽  
C Elegans ◽  
Dynein Motor ◽  
Self Association ◽  
Meiotic Synapsis

Abstract The dynein motor complex is thought to aid in homolog pairing in many organisms by moving chromosomes within the nuclear periphery to promote and test homologous interactions. This precedes synaptonemal complex (SC) formation during homolog synapsis, which stabilizes homolog proximity during recombination. We observed that depletion of the dynein light chain (DLC-1) in Caenorhabditis elegans irreversibly prevents synapsis, causing an increase in off-chromatin formation of SC protein foci with increasing temperature. This requirement for DLC-1 is independent of its function in dynein motors, as SYP protein foci do not form with depletion of other dynein motor components. In contrast to normal SC-related structures, foci formed with DLC-1 depletion are resistant to dissolution with 1,6-hexanediol, similar to aggregates of SC proteins formed in high growth temperatures. Dynein light chains have been shown to act as hub proteins that interact with other proteins through a conserved binding motif. We identified a similar DLC-1 binding motif in the C. elegans SC protein SYP-2, and mutation of the putative motif causes meiosis defects that are exacerbated by elevated temperatures. We propose that DLC-1 acts as a pre-synapsis chaperone-like factor for SYP proteins to help regulate their self-association prior to the signals for SC assembly, a role that is revealed by its increased essentiality at elevated temperatures.

scholarly journals P granules extend the nuclear pore complex environment in the C. elegans germ line

2011 ◽  
Vol 192 (6) ◽  
pp. 939-948 ◽  
Author(s):  
Dustin L. Updike ◽  
Stephanie J. Hachey ◽  
Jeremy Kreher ◽  
Susan Strome
Keyword(s):  
Nuclear Pore Complex ◽  
Germ Plasm ◽  
Germ Line ◽  
Hydrophobic Interactions ◽  
Nuclear Periphery ◽  
Size Exclusion ◽  
Nuclear Pore ◽  
Complex Environment ◽  
P Granules ◽  
C Elegans

The immortal and totipotent properties of the germ line depend on determinants within the germ plasm. A common characteristic of germ plasm across phyla is the presence of germ granules, including P granules in Caenorhabditis elegans, which are typically associated with the nuclear periphery. In C. elegans, nuclear pore complex (NPC)–like FG repeat domains are found in the VASA-related P-granule proteins GLH-1, GLH-2, and GLH-4 and other P-granule components. We demonstrate that P granules, like NPCs, are held together by weak hydrophobic interactions and establish a size-exclusion barrier. Our analysis of intestine-expressed proteins revealed that GLH-1 and its FG domain are not sufficient to form granules, but require factors like PGL-1 to nucleate the localized concentration of GLH proteins. GLH-1 is necessary but not sufficient for the perinuclear location of granules in the intestine. Our results suggest that P granules extend the NPC environment in the germ line and provide insights into the roles of the PGL and GLH family proteins.

scholarly journals Centrosome attachment to the C. elegans male pronucleus is dependent on the surface area of the nuclear envelope

2009 ◽  
Vol 327 (2) ◽  
pp. 433-446 ◽  
Author(s):  
Marina Meyerzon ◽  
Zhizhen Gao ◽  
Jin Liu ◽  
Jui-Ching Wu ◽  
Christian J. Malone ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Surface Area ◽  
Male Pronucleus ◽  
C Elegans

The expression, lamin-dependent localization and RNAi depletion phenotype for emerin inC. elegans

2002 ◽  
Vol 115 (5) ◽  
pp. 923-929 ◽  
Author(s):  
Yosef Gruenbaum ◽  
Kenneth K. Lee ◽  
Jun Liu ◽  
Merav Cohen ◽  
Katherine L. Wilson
Keyword(s):  
Nuclear Envelope ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Growth Conditions ◽  
Rnai Phenotype ◽  
Lamin B ◽  
C Elegans ◽  
Nuclear Lamins ◽  
First Time

Emerin belongs to the LEM-domain family of nuclear membrane proteins, which are conserved in metazoans from C. elegans to humans. Loss of emerin in humans causes the X-linked form of Emery-Dreifuss muscular dystrophy(EDMD), but the disease mechanism is not understood. We have begun to address the function of emerin in C. elegans, a genetically tractable nematode. The emerin gene (emr-1) is conserved in C. elegans. We detect Ce-emerin protein in the nuclear envelopes of all cell types except sperm, and find that Ce-emerin co-immunoprecipitates with Ce-lamin from embryo lysates. We show for the first time in any organism that nuclear lamins are essential for the nuclear envelope localization of emerin during early development. We further show that four other types of nuclear envelope proteins, including fellow LEM-domain protein Ce-MAN1, as well as Ce-lamin, UNC-84 and nucleoporins do not depend on Ce-emerin for their localization. This result suggests that emerin is not essential to organize or localize the only lamin (B-type) expressed in C. elegans. We also analyzed the RNAi phenotype resulting from the loss of emerin function in C. elegans under laboratory growth conditions, and found no detectable phenotype throughout development. We propose that C. elegans is an appropriate system in which to study the molecular mechanisms of emerin function in vivo.

Sequential degradation of proteins from the nuclear envelope during apoptosis

2001 ◽  
Vol 114 (20) ◽  
pp. 3643-3653 ◽  
Author(s):  
Madeleine Kihlmark ◽  
Gabriela Imreh ◽  
Einar Hallberg
Keyword(s):  
Nuclear Envelope ◽  
Apoptotic Cell ◽  
Nuclear Periphery ◽  
Condensed Chromatin ◽  
Nuclear Pore ◽  
Dependent Manner ◽  
Nuclear Pores ◽  
Double Labeling ◽  
Lamin B ◽  
Nuclear Apoptosis

We have produced new antibodies specific for the integral pore membrane protein POM121. Using these antibodies we show that during apoptosis POM121 becomes proteolytically degraded in a caspase-dependent manner. The POM121 antibodies and antibodies specific for other proteins of the nuclear envelope were used in a comparative study of nuclear apoptosis in staurosporine-treated buffalo rat liver cells. Nuclei from these cells were classified in three different stages of apoptotic progression: stage I, moderately condensed chromatin surrounded by a smooth nuclear periphery; stage II, compact patches of condensed chromatin collapsing against a smooth nuclear periphery; stage III, round compact chromatin bodies surrounded by grape-shaped nuclear periphery. We have performed double labeling immunofluorescence microscopy of individual apoptotic cells and quantitative immunoblotting analysis of total proteins from apoptotic cell cultures. The results showed that degradation of nuclear envelope marker proteins occurred in a specific order. POM121 degradation occurred surprisingly early and was initiated before nucleosomal DNA degradation could be detected using TUNEL assay and completed before clustering of the nuclear pores. POM121 was eliminated significantly more rapid compared with NUP153 (a peripheral protein located in the nucleoplasmic basket of the nuclear pore complex) and lamin B (a component of the nuclear lamina). Disappearance of NUP153 and lamin B was coincident with onset of DNA fragmentation and clustering of nuclear pores. By contrast, the peripheral NPC protein p62 was degraded much later. The results suggest that degradation of POM121 may be an important early step in propagation of nuclear apoptosis.

scholarly journals Histone H3K9 methylation promotes formation of genome compartments inCaenorhabditis elegansvia chromosome compaction and perinuclear anchoring

2020 ◽  
Vol 117 (21) ◽  
pp. 11459-11470 ◽  
Author(s):  
Qian Bian ◽  
Erika C. Anderson ◽  
Qiming Yang ◽  
Barbara J. Meyer
Keyword(s):  
Gene Expression ◽  
Nuclear Periphery ◽  
Chromosome Conformation ◽  
C Elegans ◽  
Genome Wide ◽  
Central Regions ◽  
In Trans ◽  
Genomic Regions ◽  
In Cis ◽  
Gene Expression Levels

Genomic regions preferentially associate with regions of similar transcriptional activity, partitioning genomes into active and inactive compartments within the nucleus. Here we explore mechanisms controlling genome compartment organization inCaenorhabditis elegansand investigate roles for compartments in regulating gene expression. Distal arms ofC. eleganschromosomes, which are enriched for heterochromatic histone modifications H3K9me1/me2/me3, interact with each other bothin cisandin trans,while interacting less frequently with central regions, leading to genome compartmentalization. Arms are anchored to the nuclear periphery via the nuclear envelope protein CEC-4, which binds to H3K9me. By performing genome-wide chromosome conformation capture experiments (Hi-C), we showed that eliminating H3K9me1/me2/me3 through mutations in the methyltransferase genesmet-2andset-25significantly impaired formation of inactive Arm and active Center compartments.cec-4mutations also impaired compartmentalization, but to a lesser extent. We found that H3K9me promotes compartmentalization through two distinct mechanisms: Perinuclear anchoring of chromosome arms via CEC-4 to promote theircisassociation, and an anchoring-independent mechanism that compacts individual chromosome arms. In bothmet-2 set-25andcec-4mutants, no dramatic changes in gene expression were found for genes that switched compartments or for genes that remained in their original compartment, suggesting that compartment strength does not dictate gene-expression levels. Furthermore, H3K9me, but not perinuclear anchoring, also contributes to formation of another prominent feature of chromosome organization, megabase-scale topologically associating domains on X established by the dosage compensation condensin complex. Our results demonstrate that H3K9me plays crucial roles in regulating genome organization at multiple levels.

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