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Human Molecular Genetics, 1999, Vol. 8, No. 9 1599-1610
© 1999 Oxford University Press

Article

Doublecortin, a stabilizer of microtubules

David Horesh+, Tamar Sapir+, Fiona Francis1, Sharon Grayer Wolf2, Michal Caspi, Michael Elbaum3, Jamel Chelly1 and Orly Reiner§

Department of Molecular Genetics, The Weizmann Institute of Science, 76100 Rehovot, Israel, 1Institut Cochin de Genetique Moleculaire, U129 Inserm, CHU Cochin-Port-Royal, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France and 2Electron Microscopy Unit and 3Department of Materials and Interfaces, The Weizmann Institute of Science, 76100 Rehovot, Israel

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.

+ These authors contributed equally to this work

§ To whom correspondence should be addressed. Tel: +972 8 9342319; Fax: +972 8 9344108; Email: lvreiner{at}wicc.weizmann.ac.il


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