Dyrk1A expression pattern supports specific roles of this kinase in the adult central nervous system

被引:111
作者
Martí, E
Altafaj, X
Dierssen, M
de la Luna, S
Fotaki, V
Alvarez, M
Pérez-Riba, M
Ferrer, I
Estivill, X
机构
[1] Ctr Regulacio Genom, Genes & Dis Program, Barcelona 08003, Spain
[2] Inst Recerca Oncol, Med Mol Genet Ctr, Lhospitalet De Llobregat 08907, Barcelona, Spain
[3] ICREA, Barcelona, Spain
[4] Hosp Princeps Espanya, Serv Anat Patol, Unitat Neuropatol, Lhospitalet De Llobregat 08907, Barcelona, Spain
关键词
immunohistochemistry; central nervous system; Down syndrome; primary granular cell culture; astrocyte; kinase; minibrain; Dyrk1A;
D O I
10.1016/S0006-8993(02)04069-6
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Dyrk1A and its Drosophila orthologue, the protein minibrain (mnb), belong to a family of serine/threonine kinases involved in the development of the central nervous system (CNS). However, additional roles for Dyrk1A have to be proposed, as its expression is still prominent in the adult brain. To gain insight into Dyrk1A physiological roles we have studied the distribution of this kinase in the CNS of mice in adulthood. A homogeneous diffuse immunostaining of variable intensity was detected throughout the neuropile, with the white matter displaying faint Dyrk1A immunoreactivity. Dyrk1A immunostaining was strong in the olfactory bulb, the cerebellar cortex and functionally related structures, the spinal cord and most of the motor nuclei of the midbrain and brain stem. These data agree with a possible implication of this kinase in the physiology of olfaction and motor functions. Cellular and subcellular localisation of Dyrk1A was also studied in primary cell culture of cerebellum, one of the structures showing significant Dyrk1A immunostaining in the adult. The distribution of Dyrk1A in primary cell culture showed the presence of this protein in the nucleus and the cytoplasm of both neurons and astrocytes. Moreover, studies on the subcellular distribution of Dyrk1A in whole brain homogenates of adult mice showed the presence of this protein both in nuclear and cytoplasm-enriched fractions, thus supporting selective functions of this kinase in these two subcellular compartments. The present results showing the distribution of Dyrk1A in widespread areas of the adult CNS and in different subcellular compartments, together with previous reports demonstrating its implication in developmental events concur with the idea of several spatio-temporal functional profiles. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:250 / 263
页数:14
相关论文
共 34 条
[1]   Neurodevelopmental delay, motor abnormalities and cognitive deficits in transgenic mice overexpressing Dyrk1A (minibrain), a murine model of Down's syndrome [J].
Altafaj, X ;
Dierssen, M ;
Baamonde, C ;
Martí, E ;
Visa, J ;
Guimerà, J ;
Oset, M ;
González, JR ;
Flórez, J ;
Fillat, C ;
Estivill, X .
HUMAN MOLECULAR GENETICS, 2001, 10 (18) :1915-1923
[2]   Chromosome 21: from sequence to applications [J].
Antonarakis, SE .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2001, 11 (03) :241-246
[3]   Pom1p, a fission yeast protein kinase that provides positional information for both polarized growth and cytokinesis [J].
Bähler, J ;
Pringle, JR .
GENES & DEVELOPMENT, 1998, 12 (09) :1356-1370
[4]   Sequence characteristics, subcellular localization, and substrate specificity of DYRK-related kinases, a novel family of dual specificity protein kinases [J].
Becker, W ;
Weber, Y ;
Wetzel, K ;
Eirmbter, K ;
Tejedor, FJ ;
Joost, HG .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (40) :25893-25902
[5]   Dynamin is a minibrain kinase/dual specificity Yak1-related kinase 1A substrate [J].
Chen-Hwang, MC ;
Chen, HR ;
Elzinga, M ;
Hwang, YW .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (20) :17597-17604
[6]   Dyrk1A haploinsufficiency affects viability and causes developmental delay and abnormal brain morphology in mice [J].
Fotaki, V ;
Dierssen, M ;
Alcántara, S ;
Martínez, S ;
Martí, E ;
Casas, C ;
Visa, J ;
Soriano, E ;
Estivill, X ;
Arbonés, ML .
MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (18) :6636-6647
[7]   Coactivation of secretogranin-II and BDNF genes mediated by calcium signals in mouse cerebellar granule cells [J].
Fujita, Y ;
Katagi, J ;
Tabuchi, A ;
Tsuchiya, T ;
Tsuda, M .
MOLECULAR BRAIN RESEARCH, 1999, 63 (02) :316-324
[8]   LOSS OF RAS ACTIVITY IN SACCHAROMYCES-CEREVISIAE IS SUPPRESSED BY DISRUPTIONS OF A NEW KINASE GENE, YAKI, WHOSE PRODUCT MAY ACT DOWNSTREAM OF THE CAMP-DEPENDENT PROTEIN-KINASE [J].
GARRETT, S ;
BROACH, J .
GENES & DEVELOPMENT, 1989, 3 (09) :1336-1348
[9]   THE SACCHAROMYCES-CEREVISIAE YAK1-GENE ENCODES A PROTEIN-KINASE THAT IS INDUCED BY ARREST EARLY IN THE CELL-CYCLE [J].
GARRETT, S ;
MENOLD, MM ;
BROACH, JR .
MOLECULAR AND CELLULAR BIOLOGY, 1991, 11 (08) :4045-4052
[10]   mDYRK3 kinase is expressed selectively in late erythroid progenitor cells and attenuates colony-forming unit-erythroid development [J].
Geiger, JN ;
Knudsen, GT ;
Panek, L ;
Pandit, AK ;
Yoder, MD ;
Lord, KA ;
Creasy, CL ;
Burns, BM ;
Gaines, P ;
Dillon, SB ;
Wojchowski, DM .
BLOOD, 2001, 97 (04) :901-910