Biology subjects

Pezza, R. J.

Publications and source records attributed to Pezza, R. J..

5 recordsLinked to original sources

bioRxiv2025

Kinesin drive meiotic chromosome dynamics via interaction with the KASH5-LINC complex

Telomere-led rapid prophase chromosome movements (RPMs) during meiotic prophase are critical for homologous chromosome pairing and proper meiotic progression. These movements are generated by the cytoskeleton and are transmitted to the telomeres via the LINC complex, yet the cytoplasmic components that generate these forces remain poorly defined. Among candidates of microtubule-associated motor proteins in mouse primary spermatocytes, we confirmed KIF5B as a specific interactor of the KASH5-LINC complex. Total internal reflection fluorescence microscopy and microtubule sedimentation assays performed with purified recombinant proteins suggest a direct interaction between KASH5 and KIF5B on microtubules, enhanced by MAP7, a known KIF5B-recruiting and activating cofactor. Mapping the KIF5B-binding surface of KASH5 revealed that KASH5 N-terminal EF-hand domains mediate the interaction. Further, in vivo KIF5B-KASH5 interaction and KIF5B role in RPMs are evidenced as (1) KIF5B is recruited by KASH5-SUN1 to the nuclear envelope in two different cultured somatic cell models, (2) KIF5B is telomere-associated and colocalizes with KASH5, and microtubules associated with the nuclear envelope in mouse spermatocytes, and (3) chemical inhibition of KIF5B reduces telomere-led chromosome motions. Altogether, our findings identify the KIF5B kinesin as a previously unrecognized component of the force-generating machinery that drives chromosome movement during meiotic prophase I, acting through KASH5 as a specific nuclear membrane adaptor.

cell biology↗

bioRxiv2019

PSMC3 is required for spermatogonia niche establishment in mouse spermatogenesis

Males produce millions of spermatozoa each day, which are originated from spermatogonia. Spermatogonia niche establishment and maintenance and the subsequent haploidization of spermatocytes in meiosis are hallmarks of this process. The function of the individual players and coordinated mechanisms regulating different stages of gametogenesis in mammals are not well understood. In this work we focused on the role of PSMC3 in mouse gametogenesis. We observed that Psmc3 is highly expressed in mouse testis, and it is widely expressed in different stages of gamete formation. Conditional deletion of Psmc3 results in both male and female impairment of gonad development at early pre-meiotic stages, but has no apparent effect on meiosis progression. This is likely a consequence of abnormal spermatogonia niche establishment and/or maintenance, revealed by a massive loss of undifferentiated spermatogonia. Our work defines a fundamental role of PSMC3 functions in spermatogenesis during spermatogonia development with direct implications in fertility.

developmental biology↗

bioRxiv2018

Heterochromatin and the Synaptonemal Complex Maintain Homologous Centromere Interactions in Mouse Spermatocytes

In meiosis, crossovers between homologous chromosomes link them together. This enables them to attach to microtubules of the meiotic spindle as a unit, such that the homologs will be pulled away from one another at anaphase I. Homologous pairs can sometimes fail to become linked by crossovers. In some organisms, these non-exchange partners are still able segregate properly. In several organisms, associations between the centromeres of non-exchange partners occur in meiotic prophase. These associations have been proposed to promote segregation in meiosis I. But how centromere pairing could promote subsequent proper segregation is unclear. Here we report that meiotic centromere pairing if chromosomes in mouse spermatocytes allows the formation of an association between chromosome pairs. We find that peri-centromeric heterochromatin connections tether the centromeres of chromosome pairs after dissolution of centromere paring. Our results suggest that, in mouse spermatocytes, heterochromatin maintains the association of chromosome centromeres in the absence crossing-over.

cell biology↗

bioRxiv2018

Shugoshin protects centromere pairing and promotes segregation of non-exchange partner chromosomes in meiosis

Faithful chromosome segregation during meiosis I depends upon the formation of connections between homologous chromosomes. Crossovers between homologs connect the partners allowing them to attach to the meiotic spindle as a unit, such that they migrate away from one another at anaphase I. Homologous partners also become connected by pairing of their centromeres in meiotic prophase. This centromere pairing can promote proper segregation at anaphase I of partners that have failed to become joined by a crossover. Centromere pairing is mediated by synaptonemal complex (SC) proteins that persist at the centromere when the SC disassembles. Here, using mouse spermatocyte and yeast model systems, we tested the role of shugoshin in promoting meiotic centromere pairing by protecting centromeric synaptonemal components from disassembly. The results show that shugoshin protects centromeric SC in meiotic prophase and, in anaphase, promotes the proper segregation of partner chromosomes that are not linked by a crossover. SIGNIFICANCEMeiotic crossovers form a connection between homologous chromosomes that allows them to attach to the spindle as a single unit in meiosis I. In humans, failures in this process are a leading cause of aneuploidy. A recently described process, called centromere pairing, can also help connect meiotic chromosome partners in meiosis. Homologous chromosomes become tightly joined by a structure called the synaptonemal complex (SC) in meiotic prophase. After the SC disassembles, persisting SC proteins at the centromeres mediate their pairing. Here, studies in mouse spermatocytes and yeast are used to show that the shugoshin protein helps SC components persist at centromeres and helps centromere pairing promote the proper segregation of yeast chromosomes that fail to become tethered by crossovers.

cell biology↗

bioRxiv2016

A SUMO-Ubiquitin Relay Recruits Proteasomes to Chromosome Axes to Regulate Meiotic Recombination

Meiosis produces haploid gametes through a succession of chromosomal events including pairing, synapsis and recombination. Mechanisms that orchestrate these events remain poorly understood. We found that the SUMO-modification and ubiquitin-proteasomes systems regulate the major events of meiotic prophase in mouse. Interdependent localization of SUMO, ubiquitin and proteasomes along chromosome axes was mediated largely by RNF212 and HEI10, two E3 ligases that are also essential for crossover recombination. RNF212-dependent SUMO conjugation effected a checkpoint-like process that stalls recombination by rendering the turnover of a subset of recombination factors dependent on HEI10-mediated ubiquitylation. We propose that SUMO conjugation establishes a precondition for designating crossover sites via selective protein stabilization. Thus, meiotic chromosome axes are hubs for regulated proteolysis via SUMO-dependent control of the ubiquitin-proteasome system.\n\nOne Sentence SummaryChromosomal events of meiotic prophase in mouse are regulated by proteasome-dependent protein degradation.

genetics↗