Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons.
Doublecortin (DCX) is required for normal migration of neurons into the cerebral cortex, since mutations in the human gene cause a disruption of cortical neuronal migration. To date, little is known about the distribution of DCX protein or its function. Here, we demonstrate that DCX is expressed in migrating neurons throughout the central and peripheral nervous system during embryonic and postnatal development. DCX protein localization overlaps with microtubules in cultured primary cortical neurons, and this overlapping expression is disrupted by microtubule depolymerization. DCX coassembles with brain microtubules, and recombinant DCX stimulates the polymerization of purified tubulin. Finally, overexpression of DCX in heterologous cells leads to a dramatic microtubule phenotype that is resistant to depolymerization. Therefore, DCX likely directs neuronal migration by regulating the organization and stability of microtubules.
Gleeson
J G
JG
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, Massachusetts 02115, USA.
Lin
P T
PT
Flanagan
L A
LA
Walsh
C A
CA
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D003078:Colchicine / Q000494:pharmacology; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008938:Mitosis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009479:Neuropeptides / Q000096:biosynthesis*; D010750:Phosphoproteins / Q000096:biosynthesis*; D011689:Purkinje Cells / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020318:Rats, Long-Evans; D014404:Tubulin / Q000302:isolation & purification / Q000378:metabolism
C000714328:DCX protein, human; C000714847:Dcx protein, mouse; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D010750:Phosphoproteins; D012333:RNA, Messenger; D014404:Tubulin; D003078:Colchicine