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

Scientific Reports
Baoyi ZhuKarl Swärd

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 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 ...Continue Reading

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Citations

Aug 29, 2019·American Journal of Physiology. Cell Physiology·Karl SwärdCatarina Rippe
Oct 16, 2019·Proceedings of the National Academy of Sciences of the United States of America·Henning FröhlichGudrun Rappold
Oct 11, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Marycarmen Arévalo-MartínezM Teresa Pérez-García
Sep 30, 2020·Cellular and Molecular Gastroenterology and Hepatology·Fatima DaoudSebastian Albinsson
Nov 20, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Marie-Louise BangJu Chen

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Datasets Mentioned

BETA
GSE104540

Methods Mentioned

BETA
RNA-Seq
confocal microscopy
ChIP-Seq
Fluorescence
transfection
protein assay
electrophoresis
Assay

Software Mentioned

HoloMonitor
Excel
Image Studio
NEXN
Myocd
BiKE
GraphPad Prism
Olympus CellSens Dimension
Genome Browser

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