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  • The EMBO Journal (2006) 25, 4448 - 4457
  • doi:10.1038/sj.emboj.7601335

Published online: 7 September 2006

Distinct roles of doublecortin modulating the microtubule cytoskeleton

Carolyn A Moores1, Mylène Perderiset2, Caroline Kappeler3,4,5,6, Susan Kain7, Douglas Drummond7, Stephen J Perkins8, Jamel Chelly3,4,5,6, Rob Cross7, Anne Houdusse2 and Fiona Francis3,4,5,6

  1. School of Crystallography, Birkbeck College, University of London, London, UK
  2. Motilité Structurale, Institut Curie CNRS, UMR 144, Paris, France
  3. Département de Génétique et Développement, Institut Cochin, Paris, France
  4. INSERM U567, Paris, France
  5. CNRS UMR 8104, Paris, France
  6. Université René Descartes, Paris V, Paris, France
  7. Marie Curie Research Institute, The Chart, Oxted, UK
  8. Department of Biochemistry and Molecular Biology, University College London, London, UK

Correspondence to:

Carolyn A Moores, Department of Crystallography, Birkbeck College, University of London, Malet Street, London WC1E 7HX, UK. Tel.: +44 20 7631 6858; Fax: +44 20 7631 6803; E-mail: c.moores@mail.cryst.bbk.ac.uk

Received 18 October 2005; Accepted 16 August 2006

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.

  • Keywords:

    • doublecortin,
    • lissencephaly,
    • MAPs,
    • microtubule,
    • neuron