Journal Article

Doublecortin, a Stabilizer of Microtubules

David Horesh, Tamar Sapir, Fiona Francis, Sharon Grayer Wolf, Michal Caspi, Michael Elbaum, Jamel Chelly and Orly Reiner

in Human Molecular Genetics

Volume 8, issue 9, pages 1599-1610
Published in print September 1999 | ISSN: 0964-6906
Published online September 1999 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/8.9.1599
Doublecortin, a Stabilizer of Microtubules

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X-linked lissencephaly is a severe brain malformation affecting males. Recently it has been demonstrated that the doublecortin gene is implicated in this disorder. In order to study the function of Doublecortin, we analyzed the protein upon transfection of COS cells. Doublecortin was found to bind to the microtubule cytoskeleton. In vitro assays (using biochemical methods, DIC microscopy and electron microscopy) demonstrate that Doublecortin binds microtubules directly, stabilizes them and causes bundling. In vivo assays also show that Doublecortin stabilizes microtubules and causes bundling. Doublecortin is a basic protein with an isoelectric point of 10, typical of microtubule-binding proteins. However, its sequence contains no known microtubule-binding domain(s). The results obtained in this study with Doublecortin and our previous work on another lissencephaly gene (LIS1) emphasize the central role of regulation of microtubule dynamics and stability during neuronal morphogenesis.

Journal Article.  7978 words.  Illustrated.

Subjects: Genetics and Genomics

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