A Nucleoporin Docks Protein Phosphatase 1 to Direct Meiotic Chromosome Segregation and Nuclear Assembly

Abstract

SUMMARY During M-phase entry in metazoans with open mitosis, the concerted action of mitotic kinases disassembles nuclei and promotes assembly of kinetochores—the primary microtubule attachment sites on chromosomes. At M-phase exit, these major changes in cellular architecture must be reversed. Here, we show that the conserved kinetochore-localized nucleoporin MEL-28/ELYS docks the catalytic subunit of protein phosphatase 1 (PP1c) to direct kinetochore disassembly-dependent chromosome segregation during oocyte meiosis I, and nuclear assembly during the transition from M-phase to interphase. During oocyte meiosis I, MEL-28-PP1c disassembles kinetochores in a timely manner to promote elongation of the acentrosomal spindles that segregate homologous chromosomes. During nuclear assembly, MEL-28 recruits PP1c to the periphery of decondensed chromatin where it directs formation of a functional nuclear compartment. Thus, a pool of phosphatase activity associated with a kinetochore-localized nucleoporin contributes to two key events that occur during M-phase exit in metazoans: kinetochore disassembly and nuclear reassembly.

A SUMO-Dependent Protein Network Regulates Chromosome Congression during Oocyte Meiosis

“…The RC was shown to disassemble during anaphase, so future studies are needed to address the role of SUMO proteases in RC disassembly. Interestingly, it was recently reported that protein phosphatase 1 recruitment by the nucleoporin MEL-28 directs outer kinetochore disassembly, an event required for proper meiotic chromosome segregation (Hattersley et al., 2016). We propose that PTMs, and interactions among them, will be key regulators of the highly dynamic changes that take place within the meiotic spindle.…”

Cell Biology of theCaenorhabditis elegansNucleus

“…Other dephosphorylation events are also likely to contribute to NE reassembly at the end of mitosis. For instance, it was recently reported that MEL-28 recruits the PP1 catalytic subunit GSP-2 to meiotic chromosomes to disassemble kinetochores and promote nuclear assembly (Hattersley et al 2016).…”

Employing the one-cell C. elegans embryo to study cell division processes

“…Functionally critical residues are, in the majority of cases, conserved across other species of the Caenorhabditis genus such as briggsae , brenneri , remanei and japonica . Such analysis can also reveal critical motifs required for a specific function; for example, analysis of conserved regions within the C-terminus of the nucleoporin MEL-28 revealed a docking site for protein phosphatase 1 that is critical for its function and was subsequently found to also be present in the vertebrate ortholog (Hattersley et al 2016). …”

“…above) to generating parent transgene insertions. Of note, all of the parent transgene insertions we have employed for introducing specific mutations have been validated by crossing to mutants and demonstrating rescue (Espeut et al 2012; Cheerambathur et al 2013; Lettman et al 2013; Zanin et al 2013; Moyle et al 2014; Shimanovskaya et al 2014; Kim et al 2015; Wang et al 2015; Gerson-Gurwitz et al 2016; Hattersley et al 2016; Kim et al 2017) In the case of non-essential genes, this requires a quantifiable mutant phenotype that can be used to assess functional rescue. If the transgene has been re-encoded for RNAi-resistance and RNAi-mediated depletion is associated with severe defects, transgene functionality can also be assessed using RNAi.…”

“…For example, tracking spindle pole separation has been used to analyze the mechanisms underlying load-bearing microtubule attachment formation at kinetochores (Oegema et al 2001; Desai et al 2003), while measuring chromosome distribution on the spindle helped address how microtubule attachments are stabilized prior to anaphase onset (Cheerambathur et al 2017). Generating monopolar spindles with unattached kinetochores, followed by monitoring of the time between NEBD and chromosome decondensation is useful to study spindle assembly checkpoint (SAC) signalling (Essex et al 2009; Kim et al 2017) and direct imaging of meiotic chromosome dynamics has helped identify distinct mechanisms driving chromosome alignment and segregation (Monen et al 2005; Dumont et al 2010; Hattersley et al 2016). …”