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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...

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Autores principales: Karlsson, Amelia B., Washington, Jacqueline, Dimitrova, Valentina, Hooper, Christopher, Shekhtman, Alexander, Bakowska, Joanna C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
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.
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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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