Synaptogenesis and Survival: What is the Kinetochore doing in a Postmitotic Neuron?

The proteins that form the kinetochore have an essential and much-studied role in chromosome segregation during mitosis.  They form a bridge between spindle microtubules and centromeric DNA. What then are they doing in cells like neurons that never undergo mitosis and have no need to pull chromosomes around?  In a genetic screen for mutations that affect synapse formation we encountered one kinetochore component, mis12, and subsequently found that many and perhaps all the proteins of the kinetochore complex are required for proper synapse formation.  In addition, however, loss of several kinetochore components, caused neurons to die – rapidly in vitro and more slowly in vivo.  This essential function was not dependent on microtubule interactions and was located in the nucleus rather than in the neurites. It likely reflects a novel requirement of kinetochore proteins for repair of DNA breaks in post-mitotic cells.  Because the kinetochore is the nexus of intense regulation during cell division, we suspect it will also be central to the regulation of synaptogenesis and DNA-damage responses.

Thomas Schwarz est invité par Leticia Peris et Yves Goldberg.