Disrupted-in-Schizophrenia-1 (DISC-1): Mutant Truncation Prevents Binding to NudE-like (NUDEL) and Inhibits Neurite Outgrowth
Disrupted-in-Schizophrenia-1 (DISC-1) is a gene whose mutant truncation is associated with major psychiatric illness with a predominance of schizophrenic symptomatology. We have cloned and characterized rodent DISC-1. DISC-1 expression displays pronounced developmental regulation with the highest le...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2003-01, Vol.100 (1), p.289-294 |
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| creator | Ozeki, Yuji Tomoda, Toshifumi Kleiderlein, John Kamiya, Atsushi Bord, Lyuda Fujii, Kumiko Okawa, Masako Yamada, Naoto Hatten, Mary E. Snyder, Solomon H. Ross, Christopher A. Sawa, Akira |
| description | Disrupted-in-Schizophrenia-1 (DISC-1) is a gene whose mutant truncation is associated with major psychiatric illness with a predominance of schizophrenic symptomatology. We have cloned and characterized rodent DISC-1. DISC-1 expression displays pronounced developmental regulation with the highest levels in late embryonic life when the cerebral cortex develops. In yeast two-hybrid analyses, DISC-1 interacts with a variety of cytoskeletal proteins. One of these, NudE-like (NUDEL), is associated with cortical development and is linked to LIS-1, the disease gene for a form of lissencephaly, a disorder of cortical development. The disease mutant form of DISC-1 fails to bind NUDEL. Expression of mutant, but not wild-type, DISC-1 in PC12 cells reduces neurite extension. As schizophrenia is thought to reflect defects in cortical development that are determined by cytoskeletal protein activities, the cellular disturbances we observe with mutant DISC-1 may be relevant to psychopathologic mechanisms. |
| doi_str_mv | 10.1073/pnas.0136913100 |
| format | Article |
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We have cloned and characterized rodent DISC-1. DISC-1 expression displays pronounced developmental regulation with the highest levels in late embryonic life when the cerebral cortex develops. In yeast two-hybrid analyses, DISC-1 interacts with a variety of cytoskeletal proteins. One of these, NudE-like (NUDEL), is associated with cortical development and is linked to LIS-1, the disease gene for a form of lissencephaly, a disorder of cortical development. The disease mutant form of DISC-1 fails to bind NUDEL. Expression of mutant, but not wild-type, DISC-1 in PC12 cells reduces neurite extension. As schizophrenia is thought to reflect defects in cortical development that are determined by cytoskeletal protein activities, the cellular disturbances we observe with mutant DISC-1 may be relevant to psychopathologic mechanisms.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0136913100</identifier><identifier>PMID: 12506198</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Amino acids ; Animals ; Biological Sciences ; Cell lines ; Cloning, Molecular ; COS cells ; Cysteine Endopeptidases ; DNA Primers ; Exons ; Genes ; HeLa cells ; Humans ; Mutation ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - metabolism ; Neurites ; Neurites - physiology ; Neurology ; Neurons ; PC12 cells ; Protein Binding ; Proteins ; Rats ; Recombinant Proteins - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Rodents ; Schizophrenia ; Sequence Deletion ; Serine Endopeptidases - metabolism ; Subcellular Fractions - metabolism</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2003-01, Vol.100 (1), p.289-294</ispartof><rights>Copyright 1993-2003 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Jan 7, 2003</rights><rights>Copyright © 2003, The National Academy of Sciences 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c586t-7c54eca2e99160cbe92e385a61a876ac43ef5b8398a834db9225fc91b59a2e23</citedby><cites>FETCH-LOGICAL-c586t-7c54eca2e99160cbe92e385a61a876ac43ef5b8398a834db9225fc91b59a2e23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/100/1.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3074148$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3074148$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12506198$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ozeki, Yuji</creatorcontrib><creatorcontrib>Tomoda, Toshifumi</creatorcontrib><creatorcontrib>Kleiderlein, John</creatorcontrib><creatorcontrib>Kamiya, Atsushi</creatorcontrib><creatorcontrib>Bord, Lyuda</creatorcontrib><creatorcontrib>Fujii, Kumiko</creatorcontrib><creatorcontrib>Okawa, Masako</creatorcontrib><creatorcontrib>Yamada, Naoto</creatorcontrib><creatorcontrib>Hatten, Mary E.</creatorcontrib><creatorcontrib>Snyder, Solomon H.</creatorcontrib><creatorcontrib>Ross, Christopher A.</creatorcontrib><creatorcontrib>Sawa, Akira</creatorcontrib><title>Disrupted-in-Schizophrenia-1 (DISC-1): Mutant Truncation Prevents Binding to NudE-like (NUDEL) and Inhibits Neurite Outgrowth</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Disrupted-in-Schizophrenia-1 (DISC-1) is a gene whose mutant truncation is associated with major psychiatric illness with a predominance of schizophrenic symptomatology. We have cloned and characterized rodent DISC-1. DISC-1 expression displays pronounced developmental regulation with the highest levels in late embryonic life when the cerebral cortex develops. In yeast two-hybrid analyses, DISC-1 interacts with a variety of cytoskeletal proteins. One of these, NudE-like (NUDEL), is associated with cortical development and is linked to LIS-1, the disease gene for a form of lissencephaly, a disorder of cortical development. The disease mutant form of DISC-1 fails to bind NUDEL. Expression of mutant, but not wild-type, DISC-1 in PC12 cells reduces neurite extension. As schizophrenia is thought to reflect defects in cortical development that are determined by cytoskeletal protein activities, the cellular disturbances we observe with mutant DISC-1 may be relevant to psychopathologic mechanisms.</description><subject>Amino acids</subject><subject>Animals</subject><subject>Biological Sciences</subject><subject>Cell lines</subject><subject>Cloning, Molecular</subject><subject>COS cells</subject><subject>Cysteine Endopeptidases</subject><subject>DNA Primers</subject><subject>Exons</subject><subject>Genes</subject><subject>HeLa cells</subject><subject>Humans</subject><subject>Mutation</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Neurites</subject><subject>Neurites - physiology</subject><subject>Neurology</subject><subject>Neurons</subject><subject>PC12 cells</subject><subject>Protein Binding</subject><subject>Proteins</subject><subject>Rats</subject><subject>Recombinant Proteins - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Rodents</subject><subject>Schizophrenia</subject><subject>Sequence Deletion</subject><subject>Serine Endopeptidases - metabolism</subject><subject>Subcellular Fractions - metabolism</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctvEzEYxFcIREvhzAWQxQG1h2392l0biQMkASKFFKnhbHm9TuJ0Ywc_ykPif8dRoqZwgJMP85vR-JuieIrgOYINudhYGc4hIjVHBEF4rzhGkKOyphzeL44hxE3JKKZHxaMQVhBCXjH4sDhCuII14uy4-DU0wadN1F1pbHmlluan2yy9tkaWCJwOx1eDEp29Bp9SlDaCmU9WyWicBZ-9vtE2BvDO2M7YBYgOTFM3KntzrcHp9MtwNDkD0nZgbJemNZmc6uRN1OAyxYV33-LycfFgLvugn-zfk2L2fjQbfCwnlx_Gg7eTUlWsjmWjKqqVxJpzVEPVao41YZWskWRNLRUlel61jHAmGaFdyzGu5oqjtuLZhMlJ8WYXu0ntWncq1_ayFxtv1tL_EE4a8adizVIs3I1ANF-MZv-rvd-7r0mHKNYmKN330mqXgmgwrzCh5L8gYjVhqKkz-PIvcOWSt_kGAuc5q6rGTYYudpDyLgSv57eNERTb-cV2fnGYPzte3P3ogd_vfafg1nmIy3kCMy7mqe-j_h4z-PxfYNaf7fRViM7fAgQ2FFFGfgOtz8v9</recordid><startdate>20030107</startdate><enddate>20030107</enddate><creator>Ozeki, Yuji</creator><creator>Tomoda, Toshifumi</creator><creator>Kleiderlein, John</creator><creator>Kamiya, Atsushi</creator><creator>Bord, Lyuda</creator><creator>Fujii, Kumiko</creator><creator>Okawa, Masako</creator><creator>Yamada, Naoto</creator><creator>Hatten, Mary E.</creator><creator>Snyder, Solomon H.</creator><creator>Ross, Christopher A.</creator><creator>Sawa, Akira</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><general>The National Academy of Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20030107</creationdate><title>Disrupted-in-Schizophrenia-1 (DISC-1): Mutant Truncation Prevents Binding to NudE-like (NUDEL) and Inhibits Neurite Outgrowth</title><author>Ozeki, Yuji ; 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We have cloned and characterized rodent DISC-1. DISC-1 expression displays pronounced developmental regulation with the highest levels in late embryonic life when the cerebral cortex develops. In yeast two-hybrid analyses, DISC-1 interacts with a variety of cytoskeletal proteins. One of these, NudE-like (NUDEL), is associated with cortical development and is linked to LIS-1, the disease gene for a form of lissencephaly, a disorder of cortical development. The disease mutant form of DISC-1 fails to bind NUDEL. Expression of mutant, but not wild-type, DISC-1 in PC12 cells reduces neurite extension. As schizophrenia is thought to reflect defects in cortical development that are determined by cytoskeletal protein activities, the cellular disturbances we observe with mutant DISC-1 may be relevant to psychopathologic mechanisms.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>12506198</pmid><doi>10.1073/pnas.0136913100</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amino acids Animals Biological Sciences Cell lines Cloning, Molecular COS cells Cysteine Endopeptidases DNA Primers Exons Genes HeLa cells Humans Mutation Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Neurites Neurites - physiology Neurology Neurons PC12 cells Protein Binding Proteins Rats Recombinant Proteins - metabolism Reverse Transcriptase Polymerase Chain Reaction Rodents Schizophrenia Sequence Deletion Serine Endopeptidases - metabolism Subcellular Fractions - metabolism |
| title | Disrupted-in-Schizophrenia-1 (DISC-1): Mutant Truncation Prevents Binding to NudE-like (NUDEL) and Inhibits Neurite Outgrowth |
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