Doublecortin, a stabilizer of microtubules.
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 iso-electric 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.
Horesh
D
D
Department of Molecular Genetics, The Weizmann Institute of Science, 76100 Rehovot, Israel.
Sapir
T
T
Francis
F
F
Wolf
S G
SG
Caspi
M
M
Elbaum
M
M
Chelly
J
J
Reiner
O
O
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D019556:COS Cells; D002478:Cells, Cultured; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005455:Fluorescent Antibody Technique; D051379:Mice; D008854:Microscopy, Electron; D008857:Microscopy, Interference; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D009024:Morphogenesis; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D009842:Oligopeptides; D010455:Peptides / Q000378:metabolism; D010957:Plasmids; D011485:Protein Binding; D051381:Rats; D012542:Scattering, Radiation; D014162:Transfection
C000714847:Dcx protein, mouse; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D009842:Oligopeptides; D010455:Peptides; C085706:FLAG peptide; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C513190:Pafah1b1 protein, mouse