The kinetochore proteins Ndc80 and Dsn1 are required for survival of postmitotic neurons

Abstract

Dsn1 and Ndc80 are essential proteins of the kinetochore complex and required for chromosome segregation in dividing cells and for regulating development and microtubule dynamics in postmitotic neurons. With conditional deletion of floxed alleles, we here show that Dsn1 and Ndc80 are also required for the viability of postmitotic neurons, both in cultures of hippocampal and cortical neurons and in vivo in the retina. Loss of these proteins triggers apoptosis, as indicated by caspase cleavage and an increase in nuclear DNA breakage. The pro-survival function of the kinetochore components is distinct from that which was previously demonstrated for regulation of neuronal synaptogenesis. The microtubule-binding domain of Ndc80 is required for the synaptogenic functions but Ndc80 lacking this domain can nonetheless rescue the viability of neurons from which Ndc80 has been deleted. Similarly, whereas the synaptogenic function involves regulation of microtubules in axons and dendrites, a nucleus-localized Dsn1 is sufficient to rescue the viability of neurons from which Dsn1 has been deleted. Thus, postmitotic neurons retain a nuclear requirement for components of the kinetochore in order to prevent apoptosis.