| Timothy syndrome is associated with activity-dependent dendritic retraction in rodent and human neurons. | |
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MedLine Citation:
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PMID: 23313911 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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L-type voltage gated calcium channels have an important role in neuronal development by promoting dendritic growth and arborization. A point mutation in the gene encoding Ca(V)1.2 causes Timothy syndrome, a neurodevelopmental disorder associated with autism spectrum disorders (ASDs). We report that channels with the Timothy syndrome alteration cause activity-dependent dendrite retraction in rat and mouse neurons and in induced pluripotent stem cell (iPSC)-derived neurons from individuals with Timothy syndrome. Dendrite retraction was independent of calcium permeation through the mutant channel, was associated with ectopic activation of RhoA and was inhibited by overexpression of the channel-associated GTPase Gem. These results suggest that Ca(V)1.2 can activate RhoA signaling independently of Ca(2+) and provide insights into the cellular basis of Timothy syndrome and other ASDs. |
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Authors:
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Jocelyn F Krey; Sergiu P Paşca; Aleksandr Shcheglovitov; Masayuki Yazawa; Rachel Schwemberger; Randall Rasmusson; Ricardo E Dolmetsch |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2013-01-13 |
Journal Detail:
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Title: Nature neuroscience Volume: 16 ISSN: 1546-1726 ISO Abbreviation: Nat. Neurosci. Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-01-28 Completed Date: 2013-03-22 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 9809671 Medline TA: Nat Neurosci Country: United States |
Other Details:
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Languages: eng Pagination: 201-9 Citation Subset: IM |
Affiliation:
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Department of Neurobiology, Stanford University School of Medicine, Stanford, California, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bacterial Proteins / genetics Calcium / metabolism Calcium Channels, L-Type / genetics, metabolism Cell Differentiation / drug effects, genetics Cells, Cultured Cerebral Cortex / cytology Dendrites / drug effects, pathology*, ultrastructure Disease Models, Animal Embryo, Mammalian Humans Long QT Syndrome / genetics, pathology* Luminescent Proteins / genetics Mice Myosin Light Chains / metabolism Neurons / drug effects, pathology* Photic Stimulation RNA, Small Interfering / genetics Rats Silver Staining Syndactyly / genetics, pathology* Transfection rhoA GTP-Binding Protein / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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DP1 MH099904/MH/NIMH NIH HHS; DP1 OD003889/OD/NIH HHS; F31 NS055549-03/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Bacterial Proteins; 0/Calcium Channels, L-Type; 0/L-type calcium channel alpha(1C); 0/Luminescent Proteins; 0/Mylpf protein, mouse; 0/Myosin Light Chains; 0/RNA, Small Interfering; 0/red fluorescent protein; 0/yellow fluorescent protein, Bacteria; 7440-70-2/Calcium; EC 3.6.5.2/rhoA GTP-Binding Protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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