Journal
EMBO JOURNAL
Volume 25, Issue 19, Pages 4448-4457Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.emboj.7601335
Keywords
doublecortin; lissencephaly; MAPs; microtubule; neuron
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Funding
- Biotechnology and Biological Sciences Research Council [BBS/A/00048] Funding Source: Medline
- Biotechnology and Biological Sciences Research Council [BBS/A/00048] Funding Source: researchfish
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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.
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