| The Coffin-Lowry syndrome-associated protein RSK2 and neurosecretion. | |
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MedLine Citation:
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PMID: 21061166 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Coffin-Lowry syndrome (CLS) is a syndromic form of X-linked mental retardation, characterized in male patients by psychomotor and growth retardation and various skeletal anomalies. CLS is caused by mutations in the RPS6KA3 gene, which encodes RSK2, a growth factor-regulated protein kinase. Cognitive deficiencies in CLS patients are prominent, but markedly variable in severity, even between siblings. However, the vast majority of patients are severely affected, with mental retardation ranging from moderate to profound. We used a RSK2-KO mouse model that shows no obvious brain abnormalities at the anatomical and histological levels to study the function of RSK2 in neurosecretion. Behavioral studies revealed normal motor coordination, but a profound retardation in spatial learning and a deficit in long-term spatial memory, providing evidence that RSK2 plays similar roles in mental functioning both in mice and human. We found that associative LTP at cortical inputs to the lateral amygdala was blocked in Rsk2 KO mice. Using an RNA interference rescue strategy in PC12 cells, we were able to demonstrate that RSK2 regulates catecholamine release through the phosphorylation of PLD. These results provide the first molecular evidence that RSK2 could regulate neurotransmitter release by activating PLD production of lipids required for exocytosis. |
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Authors:
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M Zeniou-Meyer; F Gambino; Mohamed-Raafet Ammar; Y Humeau; N Vitale |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cellular and molecular neurobiology Volume: 30 ISSN: 1573-6830 ISO Abbreviation: Cell. Mol. Neurobiol. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2011-01-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8200709 Medline TA: Cell Mol Neurobiol Country: United States |
Other Details:
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Languages: eng Pagination: 1401-6 Citation Subset: IM |
Affiliation:
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Département Neurotransmission and Sécrétion Neuroendocrine, Institut des Neurosciences Cellulaires et Intégratives (UPR-3212), Centre National de Recherche Scientifique and Université de Strasbourg, 5 rue Blaise Pascal, 67084 Strasbourg, France. |
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