Distinct roles of doublecortin modulating the microtubule cytoskeleton

Carolyn A. Moores, Mylène Perderiset, Caroline Kappeler, Susan Kain, Douglas Drummond, Stephen J. Perkins, Jamel Chelly, Rob Cross, Anne Houdusse, Fiona Francis

Research output: Contribution to journalArticlepeer-review

81 Citations (Scopus)

Abstract

Doublecortin is a neuronal microtubule-stabilising protein, mutations of which cause mental retardation and epilepsy in humans. How doublecortin influences microtubule dynamics, and thereby brain development, is unclear. We show here by video microscopy that purified doublecortin has no effect on the growth rate of microtubules. However, it is a potent anti-catastrophe factor that stabilises microtubules by linking adjacent protofilaments and counteracting their outward bending in depolymerising microtubules. We show that doublecortin-stabilised microtubules are substrates for kinesin translocase motors and for depolymerase kinesins. In addition, doublecortin does not itself oligomerise and does not bind to tubulin heterodimers but does nucleate microtubules. In cells, doublecortin is enriched at the distal ends of neuronal processes and our data raise the possibility that the function of doublecortin in neurons is to drive assembly and stabilisation of non-centrosomal microtubules in these doublecortin-enriched distal zones. These distinct properties combine to give doublecortin a unique function in microtubule regulation, a role that cannot be compensated for by other microtubule- stabilising proteins and nucleating factors.

Original languageEnglish
Pages (from-to)4448-4457
Number of pages10
JournalEMBO Journal
Volume25
Issue number19
DOIs
Publication statusPublished - Oct 4 2006

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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