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Distinct roles of doublecortin modulating the microtubule cytoskeleton
Author(s) -
Moores Carolyn A,
Perderiset Mylène,
Kappeler Caroline,
Kain Susan,
Drummond Douglas,
Perkins Stephen J,
Chelly Jamel,
Cross Rob,
Houdusse Anne,
Francis Fiona
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601335
Subject(s) - marie curie , art history , library science , biology , history , computer science , european union , business , economic policy
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.