| Ras and Rap signaling in synaptic plasticity and mental disorders. | |
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MedLine Citation:
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PMID: 20431046 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The Ras family GTPases (Ras, Rap1, and Rap2) and their downstream mitogen-activated protein kinases (ERK, JNK, and p38MAPK) and PI3K signaling cascades control various physiological processes. In neuronal cells, recent studies have shown that these parallel cascades signal distinct forms of AMPA-sensitive glutamate receptor trafficking during experience-dependent synaptic plasticity and adaptive behavior. Interestingly, both hypo- and hyperactivation of Ras/ Rap signaling impair the capacity of synaptic plasticity, underscoring the importance of a "happy-medium" dynamic regulation of the signaling. Moreover, accumulating reports have linked various genetic defects that either up- or down-regulate Ras/Rap signaling with several mental disorders associated with learning disability (e.g., Alzheimer's disease, Angelman syndrome, autism, cardio-facio-cutaneous syndrome, Coffin-Lowry syndrome, Costello syndrome, Cowden and Bannayan-Riley-Ruvalcaba syndromes, fragile X syndrome, neurofibromatosis type 1, Noonan syndrome, schizophrenia, tuberous sclerosis, and X-linked mental retardation), highlighting the necessity of happy-medium dynamic regulation of Ras/Rap signaling in learning behavior. Thus, the recent advances in understanding of neuronal Ras/Rap signaling provide a useful guide for developing novel treatments for mental diseases. |
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Authors:
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Ruth L Stornetta; J Julius Zhu |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Review Date: 2010-04-29 |
Journal Detail:
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Title: The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry Volume: 17 ISSN: 1089-4098 ISO Abbreviation: Neuroscientist Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-02-23 Completed Date: 2011-06-15 Revised Date: 2012-03-08 |
Medline Journal Info:
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Nlm Unique ID: 9504819 Medline TA: Neuroscientist Country: United States |
Other Details:
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Languages: eng Pagination: 54-78 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, Virginia, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Humans Mental Disorders / genetics, metabolism* Neuronal Plasticity / physiology* Signal Transduction / physiology* rap GTP-Binding Proteins / genetics, metabolism* ras Proteins / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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R01 NS051241-05/NS/NINDS NIH HHS; R01 NS053570-05/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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EC 3.6.5.2/rap GTP-Binding Proteins; EC 3.6.5.2/ras Proteins |
| Comments/Corrections | |
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