Kinetochore proteins suppress neuronal microtubule dynamics and promote dendrite regeneration

James I. Hertzler, Samantha I. Simonovitch, Richard M. Albertson, Alexis T. Weiner, Derek M.R. Nye, Melissa M. Rolls

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Kinetochores connect centromeric chromatin to spindle microtubules during mitosis. Neurons are postmitotic, so it was surprising to identify transcripts of structural kinetochore (KT) proteins and regulatory chromosome passenger complex (CPC) and spindle assembly checkpoint (SAC) proteins in Drosophila neurons after dendrite injury. To test whether these proteins function during dendrite regeneration, postmitotic RNA interference (RNAi) was performed and dendrites or axons were removed using laser microsurgery. Reduction of KT, CPC, and SAC proteins decreased dendrite regeneration without affecting axon regeneration. To understand whether neuronal functions of these proteins rely on microtubules, we analyzed microtubule behavior in uninjured neurons. The number of growing plus, but not minus, ends increased in dendrites with reduced KT, CPC, and SAC proteins, while axonal microtubules were unaffected. Increased dendritic microtubule dynamics was independent of dual leucine zipper kinase (DLK)-mediated stress but was rescued by concurrent reduction of γ-tubulin, the core microtubule nucleation protein. Reduction of γ-tubulin also rescued dendrite regeneration in backgrounds containing kinetochore RNAi transgenes. We conclude that kinetochore proteins function postmitotically in neurons to suppress dendritic microtubule dynamics by inhibiting nucleation.

Original languageEnglish (US)
Pages (from-to)2125-2138
Number of pages14
JournalMolecular biology of the cell
Volume31
Issue number19
DOIs
StatePublished - Sep 1 2020

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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