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 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.
Wegiel
Jerzy
J
Department of Developmental Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA. J_Wegiel@msn.com
Kuchna
Izabela
I
Nowicki
Krzysztof
K
Frackowiak
Janusz
J
Dowjat
Karol
K
Silverman
Wayne P
WP
Reisberg
Barry
B
DeLeon
Mony
M
Wisniewski
Thomas
T
Adayev
Tatyana
T
Chen-Hwang
Mo-Chou
MC
Hwang
Yu-Wen
YW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D000906:Antibodies; D001253:Astrocytes / Q000166:cytology / Q000201:enzymology; D015415:Biomarkers; D001921:Brain / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D002467:Cell Nucleus / Q000201:enzymology; D003593:Cytoplasm / Q000201:enzymology; D004705:Endocytosis / Q000502:physiology; D042783:Endothelial Cells / Q000201:enzymology; D004805:Ependyma / Q000201:enzymology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000201:enzymology / Q000503:physiopathology; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D017729:Presynaptic Terminals / Q000201:enzymology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases; D009435:Synaptic Transmission / Q000502:physiology; D000097603:Dyrk Kinases
D000906:Antibodies; D015415:Biomarkers; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D000097603:Dyrk Kinases