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.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Moores CA,Perderiset M,Francis F,Chelly J,Houdusse A,Milligan RA

doi

10.1016/j.molcel.2004.06.009

subject

Has Abstract

pub_date

2004-06-18 00:00:00

pages

833-9

issue

6

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(04)00329-6

journal_volume

14

pub_type

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