Form of dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A nonphosphorylated at tyrosine 145 and 147 is enriched in the nuclei of astroglial cells, adult hippocampal progenitors, and some cholinergic axon terminals
Abstract Compelling lines of evidence indicate that overexpression of dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) in subjects with trisomy 21 (Down syndrome[DS]) contributes to the abnormal structure and function of the DS brain. In the present study, we used a novel,...
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| creator | Kida, E Walus, M Jarząbek, K Palminiello, S Albertini, G Rabe, A Hwang, Y.W Golabek, A.A |
| description | Abstract Compelling lines of evidence indicate that overexpression of dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) in subjects with trisomy 21 (Down syndrome[DS]) contributes to the abnormal structure and function of the DS brain. In the present study, we used a novel, phospho-dependent antibody recognizing DYRK1A only with nonphosphorylated tyrosine 145 and 147 (DYRK1A Tyr-145/147P− ), to investigate the expression pattern of this DYRK1A species in trisomic and disomic human and mouse brains. Immunoblotting and dephosphorylation experiments demonstrated higher levels of DYRK1A Tyr-145/147P− in postnatal trisomic brains in comparison with controls (by ∼40%) than those of the DYRK1A visualized by three other N- and C-terminally directed antibodies to DYRK1A. By immunofluorescence, the immunoreactivity to DYRK1A Tyr-145/147P− was the strongest in the nuclei of astroglial cells, which contrasted with the predominantly neuronal localization of DYRK1A visualized by the three other antibodies to DYRK1A we used. In addition, DYRK1A Tyr-145/147P− was enriched in the nuclei of neuronal progenitors and newly born neurons in the adult hippocampal proliferative zone and also occurred in some cholinergic axonal terminals. Our data show a distinctive expression pattern of DYRK1A forms nonphosphorylated at Tyr-145 and Tyr-147 in the brain tissue and suggest that DS subjects may exhibit not only upregulation of total DYRK1A, but also more subtle differences in phosphorylation levels of this kinase in comparison with control individuals. |
| doi_str_mv | 10.1016/j.neuroscience.2011.08.028 |
| format | Article |
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In the present study, we used a novel, phospho-dependent antibody recognizing DYRK1A only with nonphosphorylated tyrosine 145 and 147 (DYRK1A Tyr-145/147P− ), to investigate the expression pattern of this DYRK1A species in trisomic and disomic human and mouse brains. Immunoblotting and dephosphorylation experiments demonstrated higher levels of DYRK1A Tyr-145/147P− in postnatal trisomic brains in comparison with controls (by ∼40%) than those of the DYRK1A visualized by three other N- and C-terminally directed antibodies to DYRK1A. By immunofluorescence, the immunoreactivity to DYRK1A Tyr-145/147P− was the strongest in the nuclei of astroglial cells, which contrasted with the predominantly neuronal localization of DYRK1A visualized by the three other antibodies to DYRK1A we used. In addition, DYRK1A Tyr-145/147P− was enriched in the nuclei of neuronal progenitors and newly born neurons in the adult hippocampal proliferative zone and also occurred in some cholinergic axonal terminals. Our data show a distinctive expression pattern of DYRK1A forms nonphosphorylated at Tyr-145 and Tyr-147 in the brain tissue and suggest that DS subjects may exhibit not only upregulation of total DYRK1A, but also more subtle differences in phosphorylation levels of this kinase in comparison with control individuals.</description><identifier>ISSN: 0306-4522</identifier><identifier>EISSN: 1873-7544</identifier><identifier>DOI: 10.1016/j.neuroscience.2011.08.028</identifier><identifier>PMID: 21878370</identifier><identifier>CODEN: NRSCDN</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ltd</publisher><subject>Acetylcholine - metabolism ; Adolescent ; Animals ; Antibodies ; Antibodies, Monoclonal ; Antibody Specificity ; Astrocytes ; Astrocytes - enzymology ; Biological and medical sciences ; Blotting, Western ; Brain ; brain tissue ; Cell Nucleus - enzymology ; Child ; Chromosome aberrations ; Data processing ; Dephosphorylation ; Down syndrome ; Down Syndrome - enzymology ; Dyrk Kinases ; DYRK1A ; Female ; Fluorescent Antibody Technique ; Fundamental and applied biological sciences. Psychology ; Hippocampus ; Hippocampus - enzymology ; Humans ; Immunoblotting ; Immunofluorescence ; Immunoreactivity ; Male ; Medical genetics ; Medical sciences ; Mice ; Mice, Transgenic ; Nervous system ; Neural stem cells ; Neural Stem Cells - enzymology ; Neurology ; Neurons ; Phosphorylation ; Phosphotyrosine - metabolism ; Presynapse ; Presynaptic Terminals - enzymology ; Protein Serine-Threonine Kinases - metabolism ; Protein-Tyrosine Kinases - metabolism ; Stem cells ; Structure-function relationships ; Trisomy ; Ts65Dn mice ; Tyrosine ; Vertebrates: nervous system and sense organs ; Young Adult</subject><ispartof>Neuroscience, 2011-11, Vol.195, p.112-127</ispartof><rights>IBRO</rights><rights>2011 IBRO</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c562t-a5b61b0dde8b960f2e48f6a1e85a9e28406d422fdf3798be68b34152332e5ec33</citedby><cites>FETCH-LOGICAL-c562t-a5b61b0dde8b960f2e48f6a1e85a9e28406d422fdf3798be68b34152332e5ec33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.neuroscience.2011.08.028$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27926,27927,45997</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24616280$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21878370$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kida, E</creatorcontrib><creatorcontrib>Walus, M</creatorcontrib><creatorcontrib>Jarząbek, K</creatorcontrib><creatorcontrib>Palminiello, S</creatorcontrib><creatorcontrib>Albertini, G</creatorcontrib><creatorcontrib>Rabe, A</creatorcontrib><creatorcontrib>Hwang, Y.W</creatorcontrib><creatorcontrib>Golabek, A.A</creatorcontrib><title>Form of dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A nonphosphorylated at tyrosine 145 and 147 is enriched in the nuclei of astroglial cells, adult hippocampal progenitors, and some cholinergic axon terminals</title><title>Neuroscience</title><addtitle>Neuroscience</addtitle><description>Abstract Compelling lines of evidence indicate that overexpression of dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) in subjects with trisomy 21 (Down syndrome[DS]) contributes to the abnormal structure and function of the DS brain. In the present study, we used a novel, phospho-dependent antibody recognizing DYRK1A only with nonphosphorylated tyrosine 145 and 147 (DYRK1A Tyr-145/147P− ), to investigate the expression pattern of this DYRK1A species in trisomic and disomic human and mouse brains. Immunoblotting and dephosphorylation experiments demonstrated higher levels of DYRK1A Tyr-145/147P− in postnatal trisomic brains in comparison with controls (by ∼40%) than those of the DYRK1A visualized by three other N- and C-terminally directed antibodies to DYRK1A. By immunofluorescence, the immunoreactivity to DYRK1A Tyr-145/147P− was the strongest in the nuclei of astroglial cells, which contrasted with the predominantly neuronal localization of DYRK1A visualized by the three other antibodies to DYRK1A we used. In addition, DYRK1A Tyr-145/147P− was enriched in the nuclei of neuronal progenitors and newly born neurons in the adult hippocampal proliferative zone and also occurred in some cholinergic axonal terminals. 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Psychology</topic><topic>Hippocampus</topic><topic>Hippocampus - enzymology</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Immunofluorescence</topic><topic>Immunoreactivity</topic><topic>Male</topic><topic>Medical genetics</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Nervous system</topic><topic>Neural stem cells</topic><topic>Neural Stem Cells - enzymology</topic><topic>Neurology</topic><topic>Neurons</topic><topic>Phosphorylation</topic><topic>Phosphotyrosine - metabolism</topic><topic>Presynapse</topic><topic>Presynaptic Terminals - enzymology</topic><topic>Protein Serine-Threonine Kinases - metabolism</topic><topic>Protein-Tyrosine Kinases - metabolism</topic><topic>Stem cells</topic><topic>Structure-function relationships</topic><topic>Trisomy</topic><topic>Ts65Dn mice</topic><topic>Tyrosine</topic><topic>Vertebrates: nervous system and sense organs</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kida, E</creatorcontrib><creatorcontrib>Walus, M</creatorcontrib><creatorcontrib>Jarząbek, K</creatorcontrib><creatorcontrib>Palminiello, S</creatorcontrib><creatorcontrib>Albertini, G</creatorcontrib><creatorcontrib>Rabe, A</creatorcontrib><creatorcontrib>Hwang, Y.W</creatorcontrib><creatorcontrib>Golabek, A.A</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><jtitle>Neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kida, E</au><au>Walus, M</au><au>Jarząbek, K</au><au>Palminiello, S</au><au>Albertini, G</au><au>Rabe, A</au><au>Hwang, Y.W</au><au>Golabek, A.A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Form of dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A nonphosphorylated at tyrosine 145 and 147 is enriched in the nuclei of astroglial cells, adult hippocampal progenitors, and some cholinergic axon terminals</atitle><jtitle>Neuroscience</jtitle><addtitle>Neuroscience</addtitle><date>2011-11-10</date><risdate>2011</risdate><volume>195</volume><spage>112</spage><epage>127</epage><pages>112-127</pages><issn>0306-4522</issn><eissn>1873-7544</eissn><coden>NRSCDN</coden><abstract>Abstract Compelling lines of evidence indicate that overexpression of dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) in subjects with trisomy 21 (Down syndrome[DS]) contributes to the abnormal structure and function of the DS brain. In the present study, we used a novel, phospho-dependent antibody recognizing DYRK1A only with nonphosphorylated tyrosine 145 and 147 (DYRK1A Tyr-145/147P− ), to investigate the expression pattern of this DYRK1A species in trisomic and disomic human and mouse brains. Immunoblotting and dephosphorylation experiments demonstrated higher levels of DYRK1A Tyr-145/147P− in postnatal trisomic brains in comparison with controls (by ∼40%) than those of the DYRK1A visualized by three other N- and C-terminally directed antibodies to DYRK1A. By immunofluorescence, the immunoreactivity to DYRK1A Tyr-145/147P− was the strongest in the nuclei of astroglial cells, which contrasted with the predominantly neuronal localization of DYRK1A visualized by the three other antibodies to DYRK1A we used. In addition, DYRK1A Tyr-145/147P− was enriched in the nuclei of neuronal progenitors and newly born neurons in the adult hippocampal proliferative zone and also occurred in some cholinergic axonal terminals. Our data show a distinctive expression pattern of DYRK1A forms nonphosphorylated at Tyr-145 and Tyr-147 in the brain tissue and suggest that DS subjects may exhibit not only upregulation of total DYRK1A, but also more subtle differences in phosphorylation levels of this kinase in comparison with control individuals.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>21878370</pmid><doi>10.1016/j.neuroscience.2011.08.028</doi><tpages>16</tpages></addata></record> |
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| subjects | Acetylcholine - metabolism Adolescent Animals Antibodies Antibodies, Monoclonal Antibody Specificity Astrocytes Astrocytes - enzymology Biological and medical sciences Blotting, Western Brain brain tissue Cell Nucleus - enzymology Child Chromosome aberrations Data processing Dephosphorylation Down syndrome Down Syndrome - enzymology Dyrk Kinases DYRK1A Female Fluorescent Antibody Technique Fundamental and applied biological sciences. Psychology Hippocampus Hippocampus - enzymology Humans Immunoblotting Immunofluorescence Immunoreactivity Male Medical genetics Medical sciences Mice Mice, Transgenic Nervous system Neural stem cells Neural Stem Cells - enzymology Neurology Neurons Phosphorylation Phosphotyrosine - metabolism Presynapse Presynaptic Terminals - enzymology Protein Serine-Threonine Kinases - metabolism Protein-Tyrosine Kinases - metabolism Stem cells Structure-function relationships Trisomy Ts65Dn mice Tyrosine Vertebrates: nervous system and sense organs Young Adult |
| title | Form of dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A nonphosphorylated at tyrosine 145 and 147 is enriched in the nuclei of astroglial cells, adult hippocampal progenitors, and some cholinergic axon terminals |
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