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Nexilin/NEXN controls actin polymerization in smooth muscle and is regulated by myocardin family coactivators and YAP

Zhu, Baoyi LU ; Rippe, Catarina LU ; Holmberg, Johan LU ; Zeng, Shaohua LU ; Perisic, Ljubica ; Albinsson, Sebastian LU ; Hedin, Ulf ; Uvelius, Bengt LU and Swärd, Karl LU (2018) In Scientific Reports 8(1).
Abstract

Nexilin, encoded by the NEXN gene, is expressed in striated muscle and localizes to Z-discs, influencing mechanical stability. We examined Nexilin/NEXN in smooth muscle cells (SMCs), and addressed if Nexilin localizes to dense bodies and dense bands and whether it is regulated by actin-controlled coactivators from the MRTF (MYOCD, MKL1, MKL2) and YAP/TAZ (YAP1 and WWTR1) families. NEXN expression in SMCs was comparable to that in striated muscles. Immunofluorescence and immunoelectron microscopy suggested that Nexilin localizes to dense bodies and dense bands. Correlations at the mRNA level suggested that NEXN expression might be controlled by actin polymerization. Depolymerization of actin using Latrunculin B repressed the NEXN mRNA... (More)

Nexilin, encoded by the NEXN gene, is expressed in striated muscle and localizes to Z-discs, influencing mechanical stability. We examined Nexilin/NEXN in smooth muscle cells (SMCs), and addressed if Nexilin localizes to dense bodies and dense bands and whether it is regulated by actin-controlled coactivators from the MRTF (MYOCD, MKL1, MKL2) and YAP/TAZ (YAP1 and WWTR1) families. NEXN expression in SMCs was comparable to that in striated muscles. Immunofluorescence and immunoelectron microscopy suggested that Nexilin localizes to dense bodies and dense bands. Correlations at the mRNA level suggested that NEXN expression might be controlled by actin polymerization. Depolymerization of actin using Latrunculin B repressed the NEXN mRNA and protein in bladder and coronary artery SMCs. Overexpression and knockdown supported involvement of both YAP/TAZ and MRTFs in the transcriptional control of NEXN. YAP/TAZ and MRTFs appeared equally important in bladder SMCs, whereas MRTFs dominated in vascular SMCs. Expression of NEXN was moreover reduced in situations of SMC phenotypic modulation in vivo. The proximal promoter of NEXN conferred control by MRTF-A/MKL1 and MYOCD. NEXN silencing reduced actin polymerization and cell migration, as well as SMC marker expression. NEXN targeting by actin-controlled coactivators thus amplifies SMC differentiation through the actin cytoskeleton, probably via dense bodies and dense bands.

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published
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Scientific Reports
volume
8
issue
1
article number
13025
publisher
Nature Publishing Group
external identifiers
  • scopus:85071360760
ISSN
2045-2322
DOI
10.1038/s41598-018-31328-2
language
English
LU publication?
yes
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1647e680-61da-463d-a377-309c9d7360bd
date added to LUP
2019-09-12 13:55:13
date last changed
2019-11-20 05:52:01
@article{1647e680-61da-463d-a377-309c9d7360bd,
  abstract     = {<p>Nexilin, encoded by the NEXN gene, is expressed in striated muscle and localizes to Z-discs, influencing mechanical stability. We examined Nexilin/NEXN in smooth muscle cells (SMCs), and addressed if Nexilin localizes to dense bodies and dense bands and whether it is regulated by actin-controlled coactivators from the MRTF (MYOCD, MKL1, MKL2) and YAP/TAZ (YAP1 and WWTR1) families. NEXN expression in SMCs was comparable to that in striated muscles. Immunofluorescence and immunoelectron microscopy suggested that Nexilin localizes to dense bodies and dense bands. Correlations at the mRNA level suggested that NEXN expression might be controlled by actin polymerization. Depolymerization of actin using Latrunculin B repressed the NEXN mRNA and protein in bladder and coronary artery SMCs. Overexpression and knockdown supported involvement of both YAP/TAZ and MRTFs in the transcriptional control of NEXN. YAP/TAZ and MRTFs appeared equally important in bladder SMCs, whereas MRTFs dominated in vascular SMCs. Expression of NEXN was moreover reduced in situations of SMC phenotypic modulation in vivo. The proximal promoter of NEXN conferred control by MRTF-A/MKL1 and MYOCD. NEXN silencing reduced actin polymerization and cell migration, as well as SMC marker expression. NEXN targeting by actin-controlled coactivators thus amplifies SMC differentiation through the actin cytoskeleton, probably via dense bodies and dense bands.</p>},
  author       = {Zhu, Baoyi and Rippe, Catarina and Holmberg, Johan and Zeng, Shaohua and Perisic, Ljubica and Albinsson, Sebastian and Hedin, Ulf and Uvelius, Bengt and Swärd, Karl},
  issn         = {2045-2322},
  language     = {eng},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Nexilin/NEXN controls actin polymerization in smooth muscle and is regulated by myocardin family coactivators and YAP},
  url          = {http://dx.doi.org/10.1038/s41598-018-31328-2},
  doi          = {10.1038/s41598-018-31328-2},
  volume       = {8},
  year         = {2018},
}