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VRK2A is an A-type lamin–dependent nuclear envelope kinase that phosphorylates BAF

The nuclear envelope (NE) is critical for numerous fundamental cellular functions, and mutations in several NE constituents can lead to a heterogeneous spectrum of diseases. We used proximity biotinylation to uncover new constituents of the inner nuclear membrane (INM) by comparative BioID analysis...

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Autores principales: Birendra KC, May, Danielle G., Benson, Benjamin V., Kim, Dae In, Shivega, Winnie G., Ali, Manaal H., Faustino, Randolph S., Campos, Alexandre R., Roux, Kyle J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555652/
https://www.ncbi.nlm.nih.gov/pubmed/28637768
http://dx.doi.org/10.1091/mbc.E17-03-0138
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author Birendra KC,
May, Danielle G.
Benson, Benjamin V.
Kim, Dae In
Shivega, Winnie G.
Ali, Manaal H.
Faustino, Randolph S.
Campos, Alexandre R.
Roux, Kyle J.
author_facet Birendra KC,
May, Danielle G.
Benson, Benjamin V.
Kim, Dae In
Shivega, Winnie G.
Ali, Manaal H.
Faustino, Randolph S.
Campos, Alexandre R.
Roux, Kyle J.
author_sort Birendra KC,
collection PubMed
description The nuclear envelope (NE) is critical for numerous fundamental cellular functions, and mutations in several NE constituents can lead to a heterogeneous spectrum of diseases. We used proximity biotinylation to uncover new constituents of the inner nuclear membrane (INM) by comparative BioID analysis of lamin A, Sun2 and a minimal INM-targeting motif. These studies identify vaccinia-related kinase-2 (VRK2) as a candidate constituent of the INM. The transmembrane VRK2A isoform is retained at the NE by association with A-type lamins. Furthermore, VRK2A physically interacts with A-type, but not B-type, lamins. Finally, we show that VRK2 phosphorylates barrier to autointegration factor (BAF), a small and highly dynamic chromatin-binding protein, which has roles including NE reassembly, cell cycle, and chromatin organization in cells, and subtly alters its nuclear mobility. Together these findings support the value of using BioID to identify unrecognized constituents of distinct subcellular compartments refractory to biochemical isolation and reveal VRK2A as a transmembrane kinase in the NE that regulates BAF.
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spelling pubmed-55556522017-10-30 VRK2A is an A-type lamin–dependent nuclear envelope kinase that phosphorylates BAF Birendra KC, May, Danielle G. Benson, Benjamin V. Kim, Dae In Shivega, Winnie G. Ali, Manaal H. Faustino, Randolph S. Campos, Alexandre R. Roux, Kyle J. Mol Biol Cell Brief Reports The nuclear envelope (NE) is critical for numerous fundamental cellular functions, and mutations in several NE constituents can lead to a heterogeneous spectrum of diseases. We used proximity biotinylation to uncover new constituents of the inner nuclear membrane (INM) by comparative BioID analysis of lamin A, Sun2 and a minimal INM-targeting motif. These studies identify vaccinia-related kinase-2 (VRK2) as a candidate constituent of the INM. The transmembrane VRK2A isoform is retained at the NE by association with A-type lamins. Furthermore, VRK2A physically interacts with A-type, but not B-type, lamins. Finally, we show that VRK2 phosphorylates barrier to autointegration factor (BAF), a small and highly dynamic chromatin-binding protein, which has roles including NE reassembly, cell cycle, and chromatin organization in cells, and subtly alters its nuclear mobility. Together these findings support the value of using BioID to identify unrecognized constituents of distinct subcellular compartments refractory to biochemical isolation and reveal VRK2A as a transmembrane kinase in the NE that regulates BAF. The American Society for Cell Biology 2017-08-15 /pmc/articles/PMC5555652/ /pubmed/28637768 http://dx.doi.org/10.1091/mbc.E17-03-0138 Text en © 2017 Birendra KC 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 Brief Reports
Birendra KC,
May, Danielle G.
Benson, Benjamin V.
Kim, Dae In
Shivega, Winnie G.
Ali, Manaal H.
Faustino, Randolph S.
Campos, Alexandre R.
Roux, Kyle J.
VRK2A is an A-type lamin–dependent nuclear envelope kinase that phosphorylates BAF
title VRK2A is an A-type lamin–dependent nuclear envelope kinase that phosphorylates BAF
title_full VRK2A is an A-type lamin–dependent nuclear envelope kinase that phosphorylates BAF
title_fullStr VRK2A is an A-type lamin–dependent nuclear envelope kinase that phosphorylates BAF
title_full_unstemmed VRK2A is an A-type lamin–dependent nuclear envelope kinase that phosphorylates BAF
title_short VRK2A is an A-type lamin–dependent nuclear envelope kinase that phosphorylates BAF
title_sort vrk2a is an a-type lamin–dependent nuclear envelope kinase that phosphorylates baf
topic Brief Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555652/
https://www.ncbi.nlm.nih.gov/pubmed/28637768
http://dx.doi.org/10.1091/mbc.E17-03-0138
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