Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons

被引:1111
作者
Gleeson, JG
Lin, PT
Flanagan, LA
Walsh, CA [1 ]
机构
[1] Harvard Univ, Dept Neurol, Div Neurogenet, Beth Israel Deaconess Med Ctr,Inst Med, Boston, MA 02115 USA
[2] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA
[3] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA
关键词
D O I
10.1016/S0896-6273(00)80778-3
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
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页码:257 / 271
页数:15
相关论文
共 66 条
[1]  
Anton ES, 1996, J NEUROSCI, V16, P2283
[2]   GAMMA-TUBULIN DISTRIBUTION IN THE NEURON - IMPLICATIONS FOR THE ORIGINS OF NEURITIC MICROTUBULES [J].
BAAS, PW ;
JOSHI, HC .
JOURNAL OF CELL BIOLOGY, 1992, 119 (01) :171-178
[3]   POLARITY ORIENTATION OF MICROTUBULES IN HIPPOCAMPAL-NEURONS - UNIFORMITY IN THE AXON AND NONUNIFORMITY IN THE DENDRITE [J].
BAAS, PW ;
DEITCH, JS ;
BLACK, MM ;
BANKER, GA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (21) :8335-8339
[4]   X-linked female band heterotopia-male lissencephaly syndrome [J].
Berg, MJ ;
Schifitto, G ;
Powers, JM ;
Martinez-Capolino, C ;
Fong, CT ;
Myers, GJ ;
Epstein, LG ;
Walsh, CA .
NEUROLOGY, 1998, 50 (04) :1143-1146
[5]   SOLUBILITY PROPERTIES OF NEURONAL TUBULIN - EVIDENCE FOR LABILE AND STABLE MICROTUBULES [J].
BLACK, MM ;
COCHRAN, JM ;
KURDYLA, JT .
BRAIN RESEARCH, 1984, 295 (02) :255-263
[6]   The spleen protein-tyrosine kinase TPK-IIB is highly similar to the catalytic domain of p72(syk) [J].
Brunati, AM ;
James, P ;
Guerra, B ;
Ruzzene, M ;
DonellaDeana, A ;
Pinna, LA .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1996, 240 (02) :400-407
[7]   Mice lacking p35, a neuronal specific activator of Cdk5, display cortical lamination defects, seizures, and adult lethality [J].
Chae, T ;
Kwon, YT ;
Bronson, R ;
Dikkes, P ;
Li, E ;
Tsai, LH .
NEURON, 1997, 18 (01) :29-42
[8]   A PROTEIN RELATED TO EXTRACELLULAR-MATRIX PROTEINS DELETED IN THE MOUSE MUTANT REELER [J].
DARCANGELO, G ;
MIAO, GG ;
CHEN, SC ;
SOARES, HD ;
MORGAN, JI ;
CURRAN, T .
NATURE, 1995, 374 (6524) :719-723
[9]   Nonneuronal isoforms of STOP protein are responsible for microtubule cold stability in mammalian fibroblasts [J].
Denarier, E ;
Fourest-Lieuvin, A ;
Bosc, C ;
Pirollet, F ;
Chapel, A ;
Margolis, RL ;
Job, D .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (11) :6055-6060
[10]  
des Portes V, 1998, CELL, V92, P51