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The catalytically inactive tyrosine phosphatase HD-PTP/PTPN23 is a novel regulator of SMN complex localization

The survival motor neuron (SMN) complex fulfils essential functions in the assembly of snRNPs, which are key components in the splicing of pre-mRNAs. Little is known about the regulation of SMN complex activity by posttranslational modification despite its complicated phosphorylation pattern. Severa...

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Autores principales: Husedzinovic, Alma, Neumann, Beate, Reymann, Jürgen, Draeger-Meurer, Stefanie, Chari, Ashwin, Erfle, Holger, Fischer, Utz, Gruss, Oliver J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294665/
https://www.ncbi.nlm.nih.gov/pubmed/25392300
http://dx.doi.org/10.1091/mbc.E14-06-1151
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author Husedzinovic, Alma
Neumann, Beate
Reymann, Jürgen
Draeger-Meurer, Stefanie
Chari, Ashwin
Erfle, Holger
Fischer, Utz
Gruss, Oliver J.
author_facet Husedzinovic, Alma
Neumann, Beate
Reymann, Jürgen
Draeger-Meurer, Stefanie
Chari, Ashwin
Erfle, Holger
Fischer, Utz
Gruss, Oliver J.
author_sort Husedzinovic, Alma
collection PubMed
description The survival motor neuron (SMN) complex fulfils essential functions in the assembly of snRNPs, which are key components in the splicing of pre-mRNAs. Little is known about the regulation of SMN complex activity by posttranslational modification despite its complicated phosphorylation pattern. Several phosphatases had been implicated in the regulation of SMN, including the nuclear phosphatases PPM1G and PP1γ. Here we systematically screened all human phosphatase gene products for a regulatory role in the SMN complex. We used the accumulation of SMN in Cajal bodies of intact proliferating cells, which actively assemble snRNPs, as a readout for unperturbed SMN complex function. Knockdown of 29 protein phosphatases interfered with SMN accumulation in Cajal bodies, suggesting impaired SMN complex function, among those the catalytically inactive, non–receptor-type tyrosine phosphatase PTPN23/HD-PTP. Knockdown of PTPN23 also led to changes in the phosphorylation pattern of SMN without affecting the assembly of the SMN complex. We further show interaction between SMN and PTPN23 and document that PTPN23, like SMN, shuttles between nucleus and cytoplasm. Our data provide the first comprehensive screen for SMN complex regulators and establish a novel regulatory function of PTPN23 in maintaining a highly phosphorylated state of SMN, which is important for its proper function in snRNP assembly.
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spelling pubmed-42946652015-03-30 The catalytically inactive tyrosine phosphatase HD-PTP/PTPN23 is a novel regulator of SMN complex localization Husedzinovic, Alma Neumann, Beate Reymann, Jürgen Draeger-Meurer, Stefanie Chari, Ashwin Erfle, Holger Fischer, Utz Gruss, Oliver J. Mol Biol Cell Articles The survival motor neuron (SMN) complex fulfils essential functions in the assembly of snRNPs, which are key components in the splicing of pre-mRNAs. Little is known about the regulation of SMN complex activity by posttranslational modification despite its complicated phosphorylation pattern. Several phosphatases had been implicated in the regulation of SMN, including the nuclear phosphatases PPM1G and PP1γ. Here we systematically screened all human phosphatase gene products for a regulatory role in the SMN complex. We used the accumulation of SMN in Cajal bodies of intact proliferating cells, which actively assemble snRNPs, as a readout for unperturbed SMN complex function. Knockdown of 29 protein phosphatases interfered with SMN accumulation in Cajal bodies, suggesting impaired SMN complex function, among those the catalytically inactive, non–receptor-type tyrosine phosphatase PTPN23/HD-PTP. Knockdown of PTPN23 also led to changes in the phosphorylation pattern of SMN without affecting the assembly of the SMN complex. We further show interaction between SMN and PTPN23 and document that PTPN23, like SMN, shuttles between nucleus and cytoplasm. Our data provide the first comprehensive screen for SMN complex regulators and establish a novel regulatory function of PTPN23 in maintaining a highly phosphorylated state of SMN, which is important for its proper function in snRNP assembly. The American Society for Cell Biology 2015-01-15 /pmc/articles/PMC4294665/ /pubmed/25392300 http://dx.doi.org/10.1091/mbc.E14-06-1151 Text en © 2015 Husedzinovic 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 for Cell Biology.
spellingShingle Articles
Husedzinovic, Alma
Neumann, Beate
Reymann, Jürgen
Draeger-Meurer, Stefanie
Chari, Ashwin
Erfle, Holger
Fischer, Utz
Gruss, Oliver J.
The catalytically inactive tyrosine phosphatase HD-PTP/PTPN23 is a novel regulator of SMN complex localization
title The catalytically inactive tyrosine phosphatase HD-PTP/PTPN23 is a novel regulator of SMN complex localization
title_full The catalytically inactive tyrosine phosphatase HD-PTP/PTPN23 is a novel regulator of SMN complex localization
title_fullStr The catalytically inactive tyrosine phosphatase HD-PTP/PTPN23 is a novel regulator of SMN complex localization
title_full_unstemmed The catalytically inactive tyrosine phosphatase HD-PTP/PTPN23 is a novel regulator of SMN complex localization
title_short The catalytically inactive tyrosine phosphatase HD-PTP/PTPN23 is a novel regulator of SMN complex localization
title_sort catalytically inactive tyrosine phosphatase hd-ptp/ptpn23 is a novel regulator of smn complex localization
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294665/
https://www.ncbi.nlm.nih.gov/pubmed/25392300
http://dx.doi.org/10.1091/mbc.E14-06-1151
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