The kinetochore is a multiprotein complex that connects centromeres to microtubules in meiosis and mitosis. It plays an essential role in chromosome segregation. During meiosis I, unlike in mitosis, sister kinetochores are captured by microtubules from the same spindle pole (mono-orientation) and protect centromeric cohesion mediated by cohesin protein at the onset of anaphase. These 2 kinetochore functions, mono-orientation and centromeric cohesion protection, are widely conserved among eukaryotic organisms. The mechanism for conservation is unknown.
A meiotic factor has been identified in budding and fission yeasts that regulates kinetochore function during segregation. It has been postulated that a similar factor exists in eukaryotes, but this factor-which could be the master regulator of meiotic chromosome segregation-has not been identified.
The investigators identified a meiosis-specific kinetochore factor in mouse germ cells that functions in meiosis I but not in meiosis II or mitosis. They named this factor MEIKIN (meiosis-specific kinetochore protein). MEIKIN is expressed and localized to kinetochores. Mono-orientation and cohesion protection are defective in knockout mice unable to express the MEIKIN gene. Both male and female Meikin knockout mice are infertile.
MEIKIN plays an essential role in both mono-orientation and centromeric cohesion protection, partly by stabilizing the localization of shugoshin, a protein that protects centromeric cohesin in mousemeiosis1. In mice as well as yeast, MEIKEN also regulates the activity of Polo-like kinase PLK1, which appears to be required for both kinetochore mono-orientation and centromeric cohesion protection. MEIKIN enriches PLK1 to kinetochores during segregation.
These data show that MEIKEN, a meiosis-specific kinetochore protein identified in mice, has striking biochemical and functional similarities to a regulatory factor in fission yeast. It appears to be the long-awaited master regulator of meiotic chromosome segregation conserved in living organisms from yeasts to humans. It is possible that MEIKIN dysfunction could be associated with age-associated chromosome segregation errors, a major cause of birth defects in humans.