| http://purl.uniprot.org/citations/24792215 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24792215 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24792215 | http://www.w3.org/2000/01/rdf-schema#comment | "Juvenile Batten disease (juvenile neuronal ceroid lipofuscinosis, JNCL) is a devastating neurodegenerative disease caused by mutations in CLN3, a protein of undefined function. Cell lines derived from patients or mice with CLN3 deficiency have impairments in actin-regulated processes such as endocytosis, autophagy, vesicular trafficking, and cell migration. Here we demonstrate the small GTPase Cdc42 is misregulated in the absence of CLN3, and thus may be a common link to multiple cellular defects. We discover that active Cdc42 (Cdc42-GTP) is elevated in endothelial cells from CLN3 deficient mouse brain, and correlates with enhanced PAK-1 phosphorylation, LIMK membrane recruitment, and altered actin-driven events. We also demonstrate dramatically reduced plasma membrane recruitment of the Cdc42 GTPase activating protein, ARHGAP21. In line with this, GTP-loaded ARF1, an effector of ARHGAP21 recruitment, is depressed. Together these data implicate misregulated ARF1-Cdc42 signaling as a central defect in JNCL cells, which in-turn impairs various cell functions. Furthermore our findings support concerted action of ARF1, ARHGAP21, and Cdc42 to regulate fluid phase endocytosis in mammalian cells. The ARF1-Cdc42 pathway presents a promising new avenue for JNCL therapeutic development."xsd:string |
| http://purl.uniprot.org/citations/24792215 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0096647"xsd:string |
| http://purl.uniprot.org/citations/24792215 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0096647"xsd:string |
| http://purl.uniprot.org/citations/24792215 | http://purl.uniprot.org/core/author | "Davidson B.L."xsd:string |
| http://purl.uniprot.org/citations/24792215 | http://purl.uniprot.org/core/author | "Davidson B.L."xsd:string |
| http://purl.uniprot.org/citations/24792215 | http://purl.uniprot.org/core/author | "Schultz M.L."xsd:string |
| http://purl.uniprot.org/citations/24792215 | http://purl.uniprot.org/core/author | "Schultz M.L."xsd:string |
| http://purl.uniprot.org/citations/24792215 | http://purl.uniprot.org/core/author | "Stamnes M.A."xsd:string |
| http://purl.uniprot.org/citations/24792215 | http://purl.uniprot.org/core/author | "Stamnes M.A."xsd:string |
| http://purl.uniprot.org/citations/24792215 | http://purl.uniprot.org/core/author | "Stein C.S."xsd:string |
| http://purl.uniprot.org/citations/24792215 | http://purl.uniprot.org/core/author | "Stein C.S."xsd:string |
| http://purl.uniprot.org/citations/24792215 | http://purl.uniprot.org/core/author | "Tecedor L."xsd:string |
| http://purl.uniprot.org/citations/24792215 | http://purl.uniprot.org/core/author | "Tecedor L."xsd:string |
| http://purl.uniprot.org/citations/24792215 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/24792215 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/24792215 | http://purl.uniprot.org/core/name | "PLoS ONE"xsd:string |
| http://purl.uniprot.org/citations/24792215 | http://purl.uniprot.org/core/name | "PLoS ONE"xsd:string |
| http://purl.uniprot.org/citations/24792215 | http://purl.uniprot.org/core/pages | "E96647"xsd:string |
| http://purl.uniprot.org/citations/24792215 | http://purl.uniprot.org/core/pages | "E96647"xsd:string |
| http://purl.uniprot.org/citations/24792215 | http://purl.uniprot.org/core/title | "CLN3 deficient cells display defects in the ARF1-Cdc42 pathway and actin-dependent events."xsd:string |
| http://purl.uniprot.org/citations/24792215 | http://purl.uniprot.org/core/title | "CLN3 deficient cells display defects in the ARF1-Cdc42 pathway and actin-dependent events."xsd:string |
| http://purl.uniprot.org/citations/24792215 | http://purl.uniprot.org/core/volume | "9"xsd:string |
| http://purl.uniprot.org/citations/24792215 | http://purl.uniprot.org/core/volume | "9"xsd:string |