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Endogenous spartin (SPG20) is recruited to endosomes and lipid droplets and interacts with the ubiquitin E3 ligases AIP4 and AIP5
The HSPs (hereditary spastic paraplegias) are genetic conditions in which there is distal degeneration of the longest axons of the corticospinal tract, resulting in spastic paralysis of the legs. The gene encoding spartin is mutated in Troyer syndrome, an HSP in which paralysis is accompanied by add...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Portland Press Ltd.
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2762690/ https://www.ncbi.nlm.nih.gov/pubmed/19580544 http://dx.doi.org/10.1042/BJ20082398 |
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author | Edwards, Thomas L. Clowes, Virginia E. Tsang, Hilda T. H. Connell, James W. Sanderson, Christopher M. Luzio, J. Paul Reid, Evan |
author_facet | Edwards, Thomas L. Clowes, Virginia E. Tsang, Hilda T. H. Connell, James W. Sanderson, Christopher M. Luzio, J. Paul Reid, Evan |
author_sort | Edwards, Thomas L. |
collection | PubMed |
description | The HSPs (hereditary spastic paraplegias) are genetic conditions in which there is distal degeneration of the longest axons of the corticospinal tract, resulting in spastic paralysis of the legs. The gene encoding spartin is mutated in Troyer syndrome, an HSP in which paralysis is accompanied by additional clinical features. There has been controversy over the subcellular distribution of spartin. We show here that, at steady state, endogenous spartin exists in a cytosolic pool that can be recruited to endosomes and to lipid droplets. Cytosolic endogenous spartin is mono-ubiquitinated and we demonstrate that it interacts via a PPXY motif with the ubiquitin E3 ligases AIP4 [atrophin-interacting protein 4; WWP2 (WW domain-containing E3 ubiquitin protein ligase 2] and AIP5 (WWP1). Surprisingly, the PPXY motif, AIP4 and AIP5 are not required for spartin's ubiquitination, and so we propose that spartin acts as an adaptor for these proteins. Our results suggest that spartin is involved in diverse cellular functions, which may be of relevance to the complex phenotype seen in Troyer syndrome. |
format | Text |
id | pubmed-2762690 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-27626902009-10-19 Endogenous spartin (SPG20) is recruited to endosomes and lipid droplets and interacts with the ubiquitin E3 ligases AIP4 and AIP5 Edwards, Thomas L. Clowes, Virginia E. Tsang, Hilda T. H. Connell, James W. Sanderson, Christopher M. Luzio, J. Paul Reid, Evan Biochem J Research Article The HSPs (hereditary spastic paraplegias) are genetic conditions in which there is distal degeneration of the longest axons of the corticospinal tract, resulting in spastic paralysis of the legs. The gene encoding spartin is mutated in Troyer syndrome, an HSP in which paralysis is accompanied by additional clinical features. There has been controversy over the subcellular distribution of spartin. We show here that, at steady state, endogenous spartin exists in a cytosolic pool that can be recruited to endosomes and to lipid droplets. Cytosolic endogenous spartin is mono-ubiquitinated and we demonstrate that it interacts via a PPXY motif with the ubiquitin E3 ligases AIP4 [atrophin-interacting protein 4; WWP2 (WW domain-containing E3 ubiquitin protein ligase 2] and AIP5 (WWP1). Surprisingly, the PPXY motif, AIP4 and AIP5 are not required for spartin's ubiquitination, and so we propose that spartin acts as an adaptor for these proteins. Our results suggest that spartin is involved in diverse cellular functions, which may be of relevance to the complex phenotype seen in Troyer syndrome. Portland Press Ltd. 2009-09-14 2009-10-01 /pmc/articles/PMC2762690/ /pubmed/19580544 http://dx.doi.org/10.1042/BJ20082398 Text en © 2009 The Author(s) The author(s) has paid for this article to be freely available under the terms of the Creative Commons Attribution Non-Commercial Licence (http://creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by-nc/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Edwards, Thomas L. Clowes, Virginia E. Tsang, Hilda T. H. Connell, James W. Sanderson, Christopher M. Luzio, J. Paul Reid, Evan Endogenous spartin (SPG20) is recruited to endosomes and lipid droplets and interacts with the ubiquitin E3 ligases AIP4 and AIP5 |
title | Endogenous spartin (SPG20) is recruited to endosomes and lipid droplets and interacts with the ubiquitin E3 ligases AIP4 and AIP5 |
title_full | Endogenous spartin (SPG20) is recruited to endosomes and lipid droplets and interacts with the ubiquitin E3 ligases AIP4 and AIP5 |
title_fullStr | Endogenous spartin (SPG20) is recruited to endosomes and lipid droplets and interacts with the ubiquitin E3 ligases AIP4 and AIP5 |
title_full_unstemmed | Endogenous spartin (SPG20) is recruited to endosomes and lipid droplets and interacts with the ubiquitin E3 ligases AIP4 and AIP5 |
title_short | Endogenous spartin (SPG20) is recruited to endosomes and lipid droplets and interacts with the ubiquitin E3 ligases AIP4 and AIP5 |
title_sort | endogenous spartin (spg20) is recruited to endosomes and lipid droplets and interacts with the ubiquitin e3 ligases aip4 and aip5 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2762690/ https://www.ncbi.nlm.nih.gov/pubmed/19580544 http://dx.doi.org/10.1042/BJ20082398 |
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