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The role of spartin and its novel ubiquitin binding region in DALIS occurrence
Troyer syndrome is an autosomal recessive hereditary spastic paraplegia (HSP) caused by frameshift mutations in the SPG20 gene that results in a lack of expression of the truncated protein. Spartin is a multifunctional protein, yet only two conserved domains—a microtubule-interacting and trafficking...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982999/ https://www.ncbi.nlm.nih.gov/pubmed/24523286 http://dx.doi.org/10.1091/mbc.E13-11-0705 |
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author | Karlsson, Amelia B. Washington, Jacqueline Dimitrova, Valentina Hooper, Christopher Shekhtman, Alexander Bakowska, Joanna C. |
author_facet | Karlsson, Amelia B. Washington, Jacqueline Dimitrova, Valentina Hooper, Christopher Shekhtman, Alexander Bakowska, Joanna C. |
author_sort | Karlsson, Amelia B. |
collection | PubMed |
description | Troyer syndrome is an autosomal recessive hereditary spastic paraplegia (HSP) caused by frameshift mutations in the SPG20 gene that results in a lack of expression of the truncated protein. Spartin is a multifunctional protein, yet only two conserved domains—a microtubule-interacting and trafficking domain and a plant-related senescence domain involved in cytokinesis and mitochondrial physiology, respectively—have been defined. We have shown that overexpressed spartin binds to the Ile44 hydrophobic pocket of ubiquitin, suggesting spartin might contain a ubiquitin-binding domain. In the present study, we demonstrate that spartin contributes to the formation of dendritic aggresome-like induced structures (DALIS) through a unique ubiquitin-binding region (UBR). Using short hairpin RNA, we knocked down spartin in RAW264.7 cells and found that DALIS frequency decreased; conversely, overexpression of spartin increased the percentage of cells containing DALIS. Using nuclear magnetic resonance spectroscopy, we characterized spartin's UBR and defined the UBR's amino acids that are key for ubiquitin binding. We also found that spartin, via the UBR, binds Lys-63–linked ubiquitin chains but does not bind Lys-48–linked ubiquitin chains. Finally, we demonstrate that spartin's role in DALIS formation depends on key residues within its UBR. |
format | Online Article Text |
id | pubmed-3982999 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-39829992014-06-30 The role of spartin and its novel ubiquitin binding region in DALIS occurrence Karlsson, Amelia B. Washington, Jacqueline Dimitrova, Valentina Hooper, Christopher Shekhtman, Alexander Bakowska, Joanna C. Mol Biol Cell Articles Troyer syndrome is an autosomal recessive hereditary spastic paraplegia (HSP) caused by frameshift mutations in the SPG20 gene that results in a lack of expression of the truncated protein. Spartin is a multifunctional protein, yet only two conserved domains—a microtubule-interacting and trafficking domain and a plant-related senescence domain involved in cytokinesis and mitochondrial physiology, respectively—have been defined. We have shown that overexpressed spartin binds to the Ile44 hydrophobic pocket of ubiquitin, suggesting spartin might contain a ubiquitin-binding domain. In the present study, we demonstrate that spartin contributes to the formation of dendritic aggresome-like induced structures (DALIS) through a unique ubiquitin-binding region (UBR). Using short hairpin RNA, we knocked down spartin in RAW264.7 cells and found that DALIS frequency decreased; conversely, overexpression of spartin increased the percentage of cells containing DALIS. Using nuclear magnetic resonance spectroscopy, we characterized spartin's UBR and defined the UBR's amino acids that are key for ubiquitin binding. We also found that spartin, via the UBR, binds Lys-63–linked ubiquitin chains but does not bind Lys-48–linked ubiquitin chains. Finally, we demonstrate that spartin's role in DALIS formation depends on key residues within its UBR. The American Society for Cell Biology 2014-04-15 /pmc/articles/PMC3982999/ /pubmed/24523286 http://dx.doi.org/10.1091/mbc.E13-11-0705 Text en © 2014 Karlsson et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Karlsson, Amelia B. Washington, Jacqueline Dimitrova, Valentina Hooper, Christopher Shekhtman, Alexander Bakowska, Joanna C. The role of spartin and its novel ubiquitin binding region in DALIS occurrence |
title | The role of spartin and its novel ubiquitin binding region in DALIS occurrence |
title_full | The role of spartin and its novel ubiquitin binding region in DALIS occurrence |
title_fullStr | The role of spartin and its novel ubiquitin binding region in DALIS occurrence |
title_full_unstemmed | The role of spartin and its novel ubiquitin binding region in DALIS occurrence |
title_short | The role of spartin and its novel ubiquitin binding region in DALIS occurrence |
title_sort | role of spartin and its novel ubiquitin binding region in dalis occurrence |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982999/ https://www.ncbi.nlm.nih.gov/pubmed/24523286 http://dx.doi.org/10.1091/mbc.E13-11-0705 |
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