| http://purl.uniprot.org/citations/20067919 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20067919 | http://www.w3.org/2000/01/rdf-schema#comment | "Smith-Lemli-Opitz syndrome (SLOS) is a malformation syndrome with neurocognitive deficits due to mutations of DHCR7 that impair the reduction of 7-dehydrocholesterol to cholesterol. To investigate the pathological processes underlying the neurocognitive deficits, we compared protein expression in Dhcr7(+/+) and Dhcr7(Delta3-5/Delta3-5) brain tissue. One of the proteins identified was cofilin-1, an actin depolymerizing factor which regulates neuronal dendrite and axon formation. Differential expression of cofilin-1 was due to increased phosphorylation. Phosphorylation of cofilin-1 is regulated by Rho GTPases through Rho-Rock-Limk-Cofilin-1 and Rac/Cdc42-Pak-Limk-Cofilin-1 pathways. Pull-down assays were used to demonstrate increased activation of RhoA, Rac1 and Cdc42 in Dhcr7(Delta3-5/Delta3-5) brains. Consistent with increased activation of these Rho GTPases, we observed increased phosphorylation of both Limk and Pak in mutant brain tissue. Altered Rho/Rac signaling impairs normal dendritic and axonal formation, and mutations in genes encoding regulators and effectors of the Rho GTPases underlie other human mental retardation syndromes. Thus, we hypothesized that aberrant activation of Rho/Rac could have functional consequences for dendrite and axonal growth. In vitro analysis of Dhcr7(Delta3-5/Delta3-5) hippocampal neurons demonstrated both axonal and dendritic abnormalities. Developmental abnormalities of neuronal process formation may contribute to the neurocognitive deficits found in SLOS and may represent a potential target for therapeutic intervention."xsd:string |
| http://purl.uniprot.org/citations/20067919 | http://purl.org/dc/terms/identifier | "doi:10.1093/hmg/ddq011"xsd:string |
| http://purl.uniprot.org/citations/20067919 | http://purl.uniprot.org/core/author | "Li Z."xsd:string |
| http://purl.uniprot.org/citations/20067919 | http://purl.uniprot.org/core/author | "Song L."xsd:string |
| http://purl.uniprot.org/citations/20067919 | http://purl.uniprot.org/core/author | "Yergey A.L."xsd:string |
| http://purl.uniprot.org/citations/20067919 | http://purl.uniprot.org/core/author | "Backlund P.S."xsd:string |
| http://purl.uniprot.org/citations/20067919 | http://purl.uniprot.org/core/author | "Porter F.D."xsd:string |
| http://purl.uniprot.org/citations/20067919 | http://purl.uniprot.org/core/author | "Wassif C.A."xsd:string |
| http://purl.uniprot.org/citations/20067919 | http://purl.uniprot.org/core/author | "Holtzclaw L.A."xsd:string |
| http://purl.uniprot.org/citations/20067919 | http://purl.uniprot.org/core/author | "Jiang X.S."xsd:string |
| http://purl.uniprot.org/citations/20067919 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20067919 | http://purl.uniprot.org/core/name | "Hum Mol Genet"xsd:string |
| http://purl.uniprot.org/citations/20067919 | http://purl.uniprot.org/core/pages | "1347-1357"xsd:string |
| http://purl.uniprot.org/citations/20067919 | http://purl.uniprot.org/core/title | "Activation of Rho GTPases in Smith-Lemli-Opitz syndrome: pathophysiological and clinical implications."xsd:string |
| http://purl.uniprot.org/citations/20067919 | http://purl.uniprot.org/core/volume | "19"xsd:string |
| http://purl.uniprot.org/citations/20067919 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/20067919 |
| http://purl.uniprot.org/citations/20067919 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/20067919 |
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