Analysis of meiosis in SUN1 deficient mice reveals a distinct role of SUN2 in mammalian meiotic LINC complex formation and function

PLoS Genet. 2014 Feb 27;10(2):e1004099. doi: 10.1371/journal.pgen.1004099. eCollection 2014 Feb.

Abstract

LINC complexes are evolutionarily conserved nuclear envelope bridges, composed of SUN (Sad-1/UNC-84) and KASH (Klarsicht/ANC-1/Syne/homology) domain proteins. They are crucial for nuclear positioning and nuclear shape determination, and also mediate nuclear envelope (NE) attachment of meiotic telomeres, essential for driving homolog synapsis and recombination. In mice, SUN1 and SUN2 are the only SUN domain proteins expressed during meiosis, sharing their localization with meiosis-specific KASH5. Recent studies have shown that loss of SUN1 severely interferes with meiotic processes. Absence of SUN1 provokes defective telomere attachment and causes infertility. Here, we report that meiotic telomere attachment is not entirely lost in mice deficient for SUN1, but numerous telomeres are still attached to the NE through SUN2/KASH5-LINC complexes. In Sun1(-/-) meiocytes attached telomeres retained the capacity to form bouquet-like clusters. Furthermore, we could detect significant numbers of late meiotic recombination events in Sun1(-/-) mice. Together, this indicates that even in the absence of SUN1 telomere attachment and their movement within the nuclear envelope per se can be functional.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cytoskeletal Proteins
  • Meiosis / genetics*
  • Membrane Proteins / genetics*
  • Mice
  • Microtubule-Associated Proteins / genetics*
  • Multiprotein Complexes / genetics
  • Nuclear Envelope / genetics
  • Nuclear Proteins / genetics
  • RNA, Long Noncoding / genetics*
  • Telomere / genetics
  • Telomere-Binding Proteins / genetics*

Substances

  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • KASH5 protein, mouse
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Multiprotein Complexes
  • Nuclear Proteins
  • RNA, Long Noncoding
  • SUN1 protein, mouse
  • Sun2 protein, mouse
  • Telomere-Binding Proteins

Grant support

This study was supported by the German Research Foundation (DFG, http://www.dfg.de), grant Al 1090/2-1 (Priority Program SPP1384 “Mechanisms of genome haploidization”) to MA, and the Graduate School GK1048 of the University of Würzburg (http://www.gk-1048.uni-wuerzburg.de). It received further funding by the German Research Foundation (DFG) and the University of Würzburg in the funding programme Open Access Publishing. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.