Posttranslational modifications of tubulin and the polarized transport of kinesin-1 in neurons

Jennetta W. Hammond, Chun Fang Huang, Stefanie Kaech, Catherine Jacobson, Gary Banker, Kristen J. Verhey

Research output: Contribution to journalArticle

175 Scopus citations

Abstract

Polarized transport by microtubule-based motors is critical for neuronal development and function. Selective translocation of the Kinesin-1 motor domain is the earliest known marker of axonal identity, occurring before morphological differentiation. Thus, Kinesin-1 - mediated transport may contribute to axonal specification. We tested whether posttranslational modifications of tubulin influence the ability of Kinesin-1 motors to distinguish microtubule tracks during neuronal development. We detected no difference in microtubule stability between axons and minor neurites in polarized stage 3 hippocampal neurons. In contrast, microtubule modifications were enriched in a subset of neurites in unpolarized stage 2 cells and the developing axon in polarized stage 3 cells. This enrichment correlated with the selective accumulation of constitutively active Kinesin-1 motors. Increasing tubulin acetylation, without altering the levels of other tubulin modifications, did not alter the selectivity of Kinesin-1 accumulation in polarized cells. However, globally enhancing tubulin acetylation, detyrosination, and polyglutamylation by Taxol treatment or inhibition of glycogen synthase kinase 3βdecreased the selectivity of Kinesin-1 translocation and led to the formation of multiple axons. Although microtubule acetylation enhances the motility of Kinesin-1, the preferential translocation of Kinesin-1 on axonal microtubules in polarized neuronal cells is not determined by acetylation alone but is probably specified by a combination of tubulin modifications.

Original languageEnglish (US)
Pages (from-to)572-583
Number of pages12
JournalMolecular biology of the cell
Volume21
Issue number4
DOIs
StatePublished - Feb 15 2010

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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