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Expression of TorsinA in a heterologous yeast system reveals interactions with lumenal domains of LINC and nuclear pore complex components
DYT1 dystonia is caused by an in-frame deletion of a glutamic acid codon in the gene encoding the AAA+ ATPase TorsinA (TorA). TorA localizes within the lumen of the nuclear envelope/endoplasmic reticulum and binds to a membrane-spanning cofactor, lamina associated polypeptide 1 (LAP1) or lumenal dom...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589686/ https://www.ncbi.nlm.nih.gov/pubmed/30625036 http://dx.doi.org/10.1091/mbc.E18-09-0585 |
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author | Chalfant, Madeleine Barber, Karl W. Borah, Sapan Thaller, David Lusk, C. Patrick |
author_facet | Chalfant, Madeleine Barber, Karl W. Borah, Sapan Thaller, David Lusk, C. Patrick |
author_sort | Chalfant, Madeleine |
collection | PubMed |
description | DYT1 dystonia is caused by an in-frame deletion of a glutamic acid codon in the gene encoding the AAA+ ATPase TorsinA (TorA). TorA localizes within the lumen of the nuclear envelope/endoplasmic reticulum and binds to a membrane-spanning cofactor, lamina associated polypeptide 1 (LAP1) or lumenal domain like LAP1 (LULL1), to form an ATPase; the substrate(s) of TorA remains ill-defined. Here we use budding yeast, which lack Torsins, to interrogate TorA function. We show that TorA accumulates at nuclear envelope-embedded spindle pole bodies (SPBs) in a way that requires its oligomerization and the SUN (Sad1 and UNc-84)-domain protein, Mps3. We further show that TorA physically interacts with human SUN1/2 within this system, supporting the physiological relevance of these interactions. Consistent with the idea that TorA acts on a SPB substrate, its binding to SPBs is modulated by the ATPase-stimulating activity of LAP1. TorA and TorA-ΔE reduce the fitness of cells expressing mps3 alleles, whereas TorA alone inhibits growth of cells lacking Pom152, a component of the nuclear pore complex. This genetic specificity is mirrored biochemically as TorA, but not TorA-ΔE, binds Pom152. Thus, TorA–nucleoporin interactions might be abrogated by TorA-ΔE, suggesting new experimental avenues to interrogate the molecular basis behind nuclear envelope herniations seen in mammalian cells lacking TorA function. |
format | Online Article Text |
id | pubmed-6589686 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-65896862019-07-10 Expression of TorsinA in a heterologous yeast system reveals interactions with lumenal domains of LINC and nuclear pore complex components Chalfant, Madeleine Barber, Karl W. Borah, Sapan Thaller, David Lusk, C. Patrick Mol Biol Cell Brief Report DYT1 dystonia is caused by an in-frame deletion of a glutamic acid codon in the gene encoding the AAA+ ATPase TorsinA (TorA). TorA localizes within the lumen of the nuclear envelope/endoplasmic reticulum and binds to a membrane-spanning cofactor, lamina associated polypeptide 1 (LAP1) or lumenal domain like LAP1 (LULL1), to form an ATPase; the substrate(s) of TorA remains ill-defined. Here we use budding yeast, which lack Torsins, to interrogate TorA function. We show that TorA accumulates at nuclear envelope-embedded spindle pole bodies (SPBs) in a way that requires its oligomerization and the SUN (Sad1 and UNc-84)-domain protein, Mps3. We further show that TorA physically interacts with human SUN1/2 within this system, supporting the physiological relevance of these interactions. Consistent with the idea that TorA acts on a SPB substrate, its binding to SPBs is modulated by the ATPase-stimulating activity of LAP1. TorA and TorA-ΔE reduce the fitness of cells expressing mps3 alleles, whereas TorA alone inhibits growth of cells lacking Pom152, a component of the nuclear pore complex. This genetic specificity is mirrored biochemically as TorA, but not TorA-ΔE, binds Pom152. Thus, TorA–nucleoporin interactions might be abrogated by TorA-ΔE, suggesting new experimental avenues to interrogate the molecular basis behind nuclear envelope herniations seen in mammalian cells lacking TorA function. The American Society for Cell Biology 2019-03-01 /pmc/articles/PMC6589686/ /pubmed/30625036 http://dx.doi.org/10.1091/mbc.E18-09-0585 Text en © 2019 Chalfant et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 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. |
spellingShingle | Brief Report Chalfant, Madeleine Barber, Karl W. Borah, Sapan Thaller, David Lusk, C. Patrick Expression of TorsinA in a heterologous yeast system reveals interactions with lumenal domains of LINC and nuclear pore complex components |
title | Expression of TorsinA in a heterologous yeast system reveals interactions with lumenal domains of LINC and nuclear pore complex components |
title_full | Expression of TorsinA in a heterologous yeast system reveals interactions with lumenal domains of LINC and nuclear pore complex components |
title_fullStr | Expression of TorsinA in a heterologous yeast system reveals interactions with lumenal domains of LINC and nuclear pore complex components |
title_full_unstemmed | Expression of TorsinA in a heterologous yeast system reveals interactions with lumenal domains of LINC and nuclear pore complex components |
title_short | Expression of TorsinA in a heterologous yeast system reveals interactions with lumenal domains of LINC and nuclear pore complex components |
title_sort | expression of torsina in a heterologous yeast system reveals interactions with lumenal domains of linc and nuclear pore complex components |
topic | Brief Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589686/ https://www.ncbi.nlm.nih.gov/pubmed/30625036 http://dx.doi.org/10.1091/mbc.E18-09-0585 |
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