Distinct roles of doublecortin modulating the microtubule cytoskeleton.
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.
Moores
Carolyn A
CA
School of Crystallography, Birkbeck College, University of London, London, UK. c.moores@mail.cyst.bbk.ac.uk
Perderiset
Mylène
M
Kappeler
Caroline
C
Kain
Susan
S
Drummond
Douglas
D
Perkins
Stephen J
SJ
Chelly
Jamel
J
Cross
Rob
R
Houdusse
Anne
A
Francis
Fiona
F
D000818:Animals; D001692:Biological Transport; D001696:Biomechanical Phenomena; D002417:Cattle; D002467:Cell Nucleus / Q000378:metabolism; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D006801:Humans; D016547:Kinesins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism* / Q000648:ultrastructure; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D008954:Models, Biological; D009479:Neuropeptides / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D012617:Sea Urchins; D013379:Substrate Specificity; D014404:Tubulin / Q000378:metabolism / Q000648:ultrastructure
C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D014404:Tubulin; D016547:Kinesins