Mechanism of Microtubule Stabilization by Doublecortin

Neurons undertake an amazing journey from the center of the developing mammalian brain to the outer layers of the cerebral cortex. Doublecortin, a component of the microtubule cytoskeleton, is essential in postmitotic neurons and was identified because its mutation disrupts human brain development....

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Bibliographic Details
Published in:Molecular cell 2004-06, Vol.14 (6), p.833-839
Main Authors: Moores, Carolyn A, Perderiset, Mylène, Francis, Fiona, Chelly, Jamel, Houdusse, Anne, Milligan, Ronald A
Format: Article
Language:English
Subjects:
Binding Sites
Humans
Microtubule-Associated Proteins - genetics
Microtubule-Associated Proteins - metabolism
Microtubules - metabolism
Microtubules - ultrastructure
Neuropeptides - genetics
Neuropeptides - metabolism
Tubulin - metabolism
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Summary:Neurons undertake an amazing journey from the center of the developing mammalian brain to the outer layers of the cerebral cortex. Doublecortin, a component of the microtubule cytoskeleton, is essential in postmitotic neurons and was identified because its mutation disrupts human brain development. Doublecortin stabilizes microtubules and stimulates their polymerization but has no homology with other MAPs. We used electron microscopy to characterize microtubule binding by doublecortin and visualize its binding site. Doublecortin binds selectively to 13 protofilament microtubules, its in vivo substrate, and also causes preferential assembly of 13 protofilament microtubules. This specificity was explained when we found that doublecortin binds between the protofilaments from which microtubules are built, a previously uncharacterized binding site that is ideal for microtubule stabilization. These data reveal the structural basis for doublecortin's binding selectivity and provide insight into its role in maintaining microtubule architecture in maturing neurons.
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2004.06.009