Meikin is a conserved regulator of meiosis-I-specific kinetochore function

Nature. 2015 Jan 22;517(7535):466-71. doi: 10.1038/nature14097. Epub 2014 Dec 24.

Abstract

The kinetochore is the crucial apparatus regulating chromosome segregation in mitosis and meiosis. Particularly in meiosis I, unlike in mitosis, sister kinetochores are captured by microtubules emanating from the same spindle pole (mono-orientation) and centromeric cohesion mediated by cohesin is protected in the following anaphase. Although meiotic kinetochore factors have been identified only in budding and fission yeasts, these molecules and their functions are thought to have diverged earlier. Therefore, a conserved mechanism for meiotic kinetochore regulation remains elusive. Here we have identified in mouse a meiosis-specific kinetochore factor that we termed MEIKIN, which functions in meiosis I but not in meiosis II or mitosis. MEIKIN plays a crucial role in both mono-orientation and centromeric cohesion protection, partly by stabilizing the localization of the cohesin protector shugoshin. These functions are mediated mainly by the activity of Polo-like kinase PLK1, which is enriched to kinetochores in a MEIKIN-dependent manner. Our integrative analysis indicates that the long-awaited key regulator of meiotic kinetochore function is Meikin, which is conserved from yeasts to humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / metabolism
  • Centromere / metabolism
  • Chromosomal Proteins, Non-Histone / deficiency
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Conserved Sequence*
  • Female
  • Humans
  • Infertility / genetics
  • Infertility / metabolism
  • Kinetochores / metabolism*
  • Male
  • Meiosis*
  • Mice
  • Molecular Sequence Data
  • Polo-Like Kinase 1
  • Protein Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism
  • Schizosaccharomyces pombe Proteins / metabolism

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • MEIKIN protein, mouse
  • Moa1 protein, S pombe
  • Proto-Oncogene Proteins
  • SPO13 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Schizosaccharomyces pombe Proteins
  • shugoshin protein, mouse
  • Protein Serine-Threonine Kinases

Associated data

  • GENBANK/AB987828
  • GENBANK/AB987829