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https://hdl.handle.net/2445/24657
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DC Field | Value | Language |
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dc.contributor.author | Toro, Daniel del | cat |
dc.contributor.author | Alberch i Vié, Jordi, 1959- | cat |
dc.contributor.author | Lázaro Diégez, Francisco | cat |
dc.contributor.author | Martín Ibáñez, Raquel | cat |
dc.contributor.author | Xifró i Collsamata, Xavier | cat |
dc.contributor.author | Egea Guri, Gustavo | cat |
dc.contributor.author | Canals i Coll, Josep M. | - |
dc.date.accessioned | 2012-04-27T10:17:15Z | - |
dc.date.available | 2012-04-27T10:17:15Z | - |
dc.date.issued | 2009 | - |
dc.identifier.issn | 1059-1524 | - |
dc.identifier.uri | https://hdl.handle.net/2445/24657 | - |
dc.description.abstract | Huntingtin regulates post-Golgi trafficking of secreted proteins. Here, we studied the mechanism by which mutant huntingtin impairs this process. Colocalization studies and Western blot analysis of isolated Golgi membranes showed a reduction of huntingtin in the Golgi apparatus of cells expressing mutant huntingtin. These findings correlated with a decrease in the levels of optineurin and Rab8 in the Golgi apparatus that can be reverted by overexpression of full-length wild-type huntingtin. In addition, immunoprecipitation studies showed reduced interaction between mutant huntingtin and optineurin/Rab8. Cells expressing mutant huntingtin produced both an accumulation of clathrin adaptor complex 1 at the Golgi and an increase of clathrin-coated vesicles in the vicinity of Golgi cisternae as revealed by electron microscopy. Furthermore, inverse fluorescence recovery after photobleaching analysis for lysosomal-associated membrane protein-1 and mannose-6-phosphate receptor showed that the optineurin/Rab8-dependent post-Golgi trafficking to lysosomes was impaired in cells expressing mutant huntingtin or reducing huntingtin levels by small interfering RNA. Accordingly, these cells showed a lower content of cathepsin D in lysosomes, which led to an overall reduction of lysosomal activity. Together, our results indicate that mutant huntingtin perturbs post-Golgi trafficking to lysosomal compartments by delocalizing the optineurin/Rab8 complex, which, in turn, affects the lysosomal function. | eng |
dc.format.extent | 15 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | American Society for Cell Biology | - |
dc.relation.isformatof | Reproducció del document publicat a: http://dx.doi.org/10.1091/mbc.E08-07-0726 | - |
dc.relation.ispartof | Molecular Biology of the Cell, 2009, vol. 20, núm. 5, p. 1478-1492 | - |
dc.relation.uri | http://dx.doi.org/10.1091/mbc.E08-07-0726 | - |
dc.rights | cc-by-nc-sa (c) Toro et al., 2009 | - |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/3.0/ | - |
dc.source | Articles publicats en revistes (Biomedicina) | - |
dc.subject.classification | Aparell de Golgi | cat |
dc.subject.classification | Citogenètica | cat |
dc.subject.classification | Proteïnes | cat |
dc.subject.classification | Citologia | cat |
dc.subject.other | Golgi apparatus | eng |
dc.subject.other | Cytogenetics | eng |
dc.subject.other | Proteins | eng |
dc.subject.other | Cytology | eng |
dc.title | Mutant Huntingtin impairs post-Golgi trafficking to lysosomes by delocalizing optineurin/Rab8 complex from the Golgi apparatus | eng |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 569909 | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 19144827 | - |
Appears in Collections: | Articles publicats en revistes (Biomedicina) |
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569909.pdf | 1.36 MB | Adobe PDF | View/Open |
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