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.
journal_name
Mol Celljournal_title
Molecular cellauthors
Moores CA,Perderiset M,Francis F,Chelly J,Houdusse A,Milligan RAdoi
10.1016/j.molcel.2004.06.009subject
Has Abstractpub_date
2004-06-18 00:00:00pages
833-9issue
6eissn
1097-2765issn
1097-4164pii
S1097-2765(04)00329-6journal_volume
14pub_type
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