Cell type- and brain structure-specific patterns of distribution of minibrain kinase in human brain

The minibrain kinase (Mnb/Dyrk1A) gene is localized in the Down syndrome (DS) critical region of chromosome 21. This gene encodes a proline-directed serine/threonine protein kinase (minibrain kinase-Mnb/Dyrk1A), which is required for the proliferation of distinct neuronal cell types during postembry...

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Veröffentlicht in:Brain research 2004-06, Vol.1010 (1), p.69-80
Hauptverfasser: Wegiel, Jerzy, Kuchna, Izabela, Nowicki, Krzysztof, Frackowiak, Janusz, Dowjat, Karol, Silverman, Wayne P, Reisberg, Barry, deLeon, Mony, Wisniewski, Thomas, Adayev, Tatyana, Chen-Hwang, Mo-Chou, Hwang, Yu-Wen
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container_issue 1
container_start_page 69
container_title Brain research
container_volume 1010
creator Wegiel, Jerzy
Kuchna, Izabela
Nowicki, Krzysztof
Frackowiak, Janusz
Dowjat, Karol
Silverman, Wayne P
Reisberg, Barry
deLeon, Mony
Wisniewski, Thomas
Adayev, Tatyana
Chen-Hwang, Mo-Chou
Hwang, Yu-Wen
description The minibrain kinase (Mnb/Dyrk1A) gene is localized in the Down syndrome (DS) critical region of chromosome 21. This gene encodes a proline-directed serine/threonine protein kinase (minibrain kinase-Mnb/Dyrk1A), which is required for the proliferation of distinct neuronal cell types during postembryonic neurogenesis. To study the distribution of Mnb/Dyrk1A during human brain development and aging, we raised Mnb/Dyrk1A-specific antibody (mAb 7F3) and examined 22 brains of normal subjects from 8 months to 90 years of age. We found that neurons were the only cells showing the presence of 7F3-positive product in both cell nucleus and cytoplasm. Nuclear localization supports the concept that Mnb/Dyrk1A may be involved in control of gene expression. Synaptic localization of Mnb/Dyrk1A also supports our previous studies suggesting that Mnb/Dyrk1A is a regulator of assembly of endocytic apparatus and appears to be involved in synaptic vesicle recycling and synaptic signal transmission. Accumulation of numerous 7F3-positive corpora amylacea in the memory and motor system subdivisions in subjects older than 33 years of age indicates that Mnb/Dyrk1A is colocalized with markers of astrocyte and neuron degeneration. Differences in the topography and the amount of Mnb/Dyrk1A in neurons, astrocytes, and ependymal and endothelial cells appear to reflect cell type- and brain structure-specific patterns in trafficking and utilization of Mnb/Dyrk1A.
doi_str_mv 10.1016/j.brainres.2004.03.008
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This gene encodes a proline-directed serine/threonine protein kinase (minibrain kinase-Mnb/Dyrk1A), which is required for the proliferation of distinct neuronal cell types during postembryonic neurogenesis. To study the distribution of Mnb/Dyrk1A during human brain development and aging, we raised Mnb/Dyrk1A-specific antibody (mAb 7F3) and examined 22 brains of normal subjects from 8 months to 90 years of age. We found that neurons were the only cells showing the presence of 7F3-positive product in both cell nucleus and cytoplasm. Nuclear localization supports the concept that Mnb/Dyrk1A may be involved in control of gene expression. Synaptic localization of Mnb/Dyrk1A also supports our previous studies suggesting that Mnb/Dyrk1A is a regulator of assembly of endocytic apparatus and appears to be involved in synaptic vesicle recycling and synaptic signal transmission. Accumulation of numerous 7F3-positive corpora amylacea in the memory and motor system subdivisions in subjects older than 33 years of age indicates that Mnb/Dyrk1A is colocalized with markers of astrocyte and neuron degeneration. Differences in the topography and the amount of Mnb/Dyrk1A in neurons, astrocytes, and ependymal and endothelial cells appear to reflect cell type- and brain structure-specific patterns in trafficking and utilization of Mnb/Dyrk1A.</abstract><cop>London</cop><cop>Amsterdam</cop><cop>New York, NY</cop><pub>Elsevier B.V</pub><pmid>15126119</pmid><doi>10.1016/j.brainres.2004.03.008</doi><tpages>12</tpages></addata></record>
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subjects Adult
Aged
Aged, 80 and over
Aging - metabolism
Antibodies
Astrocytes - cytology
Astrocytes - enzymology
Biological and medical sciences
Biomarkers
Brain - cytology
Brain - enzymology
Brain - growth & development
Brain aging
Brain development
Cell Nucleus - enzymology
Chromosome aberrations
Corpora amylacea
Cytoplasm - enzymology
Dyrk Kinases
Endocytosis - physiology
Endothelial Cells - enzymology
Ependyma - enzymology
Female
Humans
Immunocytochemistry
Infant
Male
Medical genetics
Medical sciences
Middle Aged
Minibrain kinase
Nerve Degeneration - enzymology
Nerve Degeneration - physiopathology
Neurons - cytology
Neurons - enzymology
Presynaptic Terminals - enzymology
Protein Serine-Threonine Kinases - metabolism
Protein-Tyrosine Kinases
Synapse
Synaptic Transmission - physiology
title Cell type- and brain structure-specific patterns of distribution of minibrain kinase in human brain
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