The X-linked mental retardation protein oligophrenin-1 is required for dendritic spine morphogenesis.
Of 11 genes involved in nonspecific X-linked mental retardation (MRX), three encode regulators or effectors of the Rho GTPases, suggesting an important role for Rho signaling in cognitive function. It remains unknown, however, how mutations in Rho-linked genes lead to MRX. Here we report that oligop...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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2004
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| _version_ | 1826277250062876672 |
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| author | Govek, E Newey, S Akerman, C Cross, JR Van der Veken, L Van Aelst, L |
| author_facet | Govek, E Newey, S Akerman, C Cross, JR Van der Veken, L Van Aelst, L |
| author_sort | Govek, E |
| collection | OXFORD |
| description | Of 11 genes involved in nonspecific X-linked mental retardation (MRX), three encode regulators or effectors of the Rho GTPases, suggesting an important role for Rho signaling in cognitive function. It remains unknown, however, how mutations in Rho-linked genes lead to MRX. Here we report that oligophrenin-1, a Rho-GTPase activating protein that is absent in a family affected with MRX, is required for dendritic spine morphogenesis. Using RNA interference and antisense RNA approaches, we show that knock-down of oligophrenin-1 levels in CA1 neurons in rat hippocampal slices significantly decreases spine length. This phenotype can be recapitulated using an activated form of RhoA and rescued by inhibiting Rho-kinase, indicating that reduced oligophrenin-1 levels affect spine length by increasing RhoA and Rho-kinase activities. We further demonstrate an interaction between oligophrenin-1 and the postsynaptic adaptor protein Homer. Our findings provide the first insight into how mutations in a Rho-linked MRX gene may compromise neuronal function. |
| first_indexed | 2024-03-06T23:26:04Z |
| format | Journal article |
| id | oxford-uuid:6a6a48c9-744b-440b-b9a2-6b39734c3420 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:26:04Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:6a6a48c9-744b-440b-b9a2-6b39734c34202022-03-26T18:57:18ZThe X-linked mental retardation protein oligophrenin-1 is required for dendritic spine morphogenesis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6a6a48c9-744b-440b-b9a2-6b39734c3420EnglishSymplectic Elements at Oxford2004Govek, ENewey, SAkerman, CCross, JRVan der Veken, LVan Aelst, LOf 11 genes involved in nonspecific X-linked mental retardation (MRX), three encode regulators or effectors of the Rho GTPases, suggesting an important role for Rho signaling in cognitive function. It remains unknown, however, how mutations in Rho-linked genes lead to MRX. Here we report that oligophrenin-1, a Rho-GTPase activating protein that is absent in a family affected with MRX, is required for dendritic spine morphogenesis. Using RNA interference and antisense RNA approaches, we show that knock-down of oligophrenin-1 levels in CA1 neurons in rat hippocampal slices significantly decreases spine length. This phenotype can be recapitulated using an activated form of RhoA and rescued by inhibiting Rho-kinase, indicating that reduced oligophrenin-1 levels affect spine length by increasing RhoA and Rho-kinase activities. We further demonstrate an interaction between oligophrenin-1 and the postsynaptic adaptor protein Homer. Our findings provide the first insight into how mutations in a Rho-linked MRX gene may compromise neuronal function. |
| spellingShingle | Govek, E Newey, S Akerman, C Cross, JR Van der Veken, L Van Aelst, L The X-linked mental retardation protein oligophrenin-1 is required for dendritic spine morphogenesis. |
| title | The X-linked mental retardation protein oligophrenin-1 is required for dendritic spine morphogenesis. |
| title_full | The X-linked mental retardation protein oligophrenin-1 is required for dendritic spine morphogenesis. |
| title_fullStr | The X-linked mental retardation protein oligophrenin-1 is required for dendritic spine morphogenesis. |
| title_full_unstemmed | The X-linked mental retardation protein oligophrenin-1 is required for dendritic spine morphogenesis. |
| title_short | The X-linked mental retardation protein oligophrenin-1 is required for dendritic spine morphogenesis. |
| title_sort | x linked mental retardation protein oligophrenin 1 is required for dendritic spine morphogenesis |
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