Chromosome Movements Promoted by the Mitochondrial Protein SPD-3 Are Required for Homology Search during Caenorhabditis elegans Meiosis

Leticia Labrador,Donald G Moerman,Thomas Müller-Reichert,Stephane Flibotte,James Lightfoot,Enrique Martinez-Perez,Anne M Villeneuve,Consuelo Barroso,Jon Taylor,Mónica P Colaiácovo

doi:10.1371/journal.pgen.1003497

Abstract

Pairing of homologous chromosomes during early meiosis is essential to prevent the formation of aneuploid gametes. Chromosome pairing includes a step of homology search followed by the stabilization of homolog interactions by the synaptonemal complex (SC). These events coincide with dramatic changes in nuclear organization and rapid chromosome movements that depend on cytoskeletal motors and are mediated by SUN-domain proteins on the nuclear envelope, but how chromosome mobility contributes to the pairing process remains poorly understood. We show that defects in the mitochondria-localizing protein SPD-3 cause a defect in homolog pairing without impairing nuclear reorganization or SC assembly, which results in promiscuous installation of the SC between non-homologous chromosomes. Preventing SC assembly in spd-3 mutants does not improve homolog pairing, demonstrating that SPD-3 is required for homology search at the start of meiosis. Pairing center regions localize to SUN-1 aggregates at meiosis onset in spd-3 mutants; and pairing-promoting proteins, including cytoskeletal motors and polo-like kinase 2, are normally recruited to the nuclear envelope. However, quantitative analysis of SUN-1 aggregate movement in spd-3 mutants demonstrates a clear reduction in mobility, although this defect is not as severe as that seen in sun-1(jf18) mutants, which also show a stronger pairing defect, suggesting a correlation between chromosome-end mobility and the efficiency of pairing. SUN-1 aggregate movement is also impaired following inhibition of mitochondrial respiration or dynein knockdown, suggesting that mitochondrial function is required for motor-driven SUN-1 movement. The reduced chromosome-end mobility of spd-3 mutants impairs coupling of SC assembly to homology recognition and causes a delay in meiotic progression mediated by HORMA-domain protein HTP-1. Our work reveals how chromosome mobility impacts the different early meiotic events that promote homolog pairing and suggests that efficient homology search at the onset of meiosis is largely dependent on motor-driven chromosome movement.

Highlights

Accurate chromosome segregation during meiosis requires the formation of physical attachments between homologous chromosomes
Western blot analysis demonstrated that protein extracts from me85 mutants lacked a band at the expected molecular weight for SPD-3, while SPD-3-positive bands were clearly visible in extracts from wild-type worms and from worms carrying the spd-3::GFP transgene (Figure 1C)
We have shown that defects in the mitochondria-localizing protein SPD-3 cause a severe reduction in the mobility of SUN-1 aggregates at the start of meiotic prophase

Summary

Introduction

Accurate chromosome segregation during meiosis requires the formation of physical attachments between homologous chromosomes (homologs). A series of events unfold during meiotic prophase to promote the formation of inter-homolog crossover events during meiotic recombination [1]. In most organisms the pairing process can be divided into three phases that have distinctive genetic requirements: the initial encounters between the homologs, during which homology recognition must take place, the stabilization of these early interactions by recombination dependent or independent mechanisms, and the assembly of the synaptonemal complex (SC) in the interface between the homologs [3]. In haploid plants or yeast the SC is promiscuously assembled between non-homologous chromosomes [4,5], and yeast, Caenorhabditis elegans and mice mutants that lack components of the central region of the SC achieve high levels of pairing [6,7,8].

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Results

Conclusion