title: Mechanism of microtubule stabilization by doublecortin.
abstract: 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.
authors.affiliation: Department of Cell Biology, CB227, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Moores
authors.forename: Mylène
authors.initials: M
authors.lastname: Perderiset
authors.forename: Fiona
authors.initials: F
authors.lastname: Francis
authors.forename: Jamel
authors.initials: J
authors.lastname: Chelly
authors.forename: Anne
authors.initials: A
authors.lastname: Houdusse
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Milligan
mesh_terms: D001665:Binding Sites; D000089622:Doublecortin Domain Proteins; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism
chemical_list: D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D014404:Tubulin