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Open AccessArticle

SUN1/2 Are Essential for RhoA/ROCK-Regulated Actomyosin Activity in Isolated Vascular Smooth Muscle Cells

1
British Heart Foundation Centre of Research Excellence, Cardiovascular Division, King’s College London, London SE5 9NU, UK
2
School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK
3
School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK
4
Randall Division of Cell and Molecular Biophysics, New Hunt’s House, King’s College London, London SE1 1YR, UK
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(1), 132; https://doi.org/10.3390/cells9010132 (registering DOI)
Received: 28 November 2019 / Revised: 20 December 2019 / Accepted: 20 December 2019 / Published: 6 January 2020
(This article belongs to the Collection Lamins and Laminopathies)
Vascular smooth muscle cells (VSMCs) are the predominant cell type in the blood vessel wall. Changes in VSMC actomyosin activity and morphology are prevalent in cardiovascular disease. The actin cytoskeleton actively defines cellular shape and the LInker of Nucleoskeleton and Cytoskeleton (LINC) complex, comprised of nesprin and the Sad1p, UNC-84 (SUN)-domain family members SUN1/2, has emerged as a key regulator of actin cytoskeletal organisation. Although SUN1 and SUN2 function is partially redundant, they possess specific functions and LINC complex composition is tailored for cell-type-specific functions. We investigated the importance of SUN1 and SUN2 in regulating actomyosin activity and cell morphology in VSMCs. We demonstrate that siRNA-mediated depletion of either SUN1 or SUN2 altered VSMC spreading and impaired actomyosin activity and RhoA activity. Importantly, these findings were recapitulated using aortic VSMCs isolated from wild-type and SUN2 knockout (SUN2 KO) mice. Inhibition of actomyosin activity, using the rho-associated, coiled-coil-containing protein kinase1/2 (ROCK1/2) inhibitor Y27632 or blebbistatin, reduced SUN2 mobility in the nuclear envelope and decreased the association between SUN2 and lamin A, confirming that SUN2 dynamics and interactions are influenced by actomyosin activity. We propose that the LINC complex exists in a mechanical feedback circuit with RhoA to regulate VSMC actomyosin activity and morphology. View Full-Text
Keywords: LINC complex; RhoA; actomyosin LINC complex; RhoA; actomyosin
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Porter, L.; Minaisah, R.-M.; Ahmed, S.; Ali, S.; Norton, R.; Zhang, Q.; Ferraro, E.; Molenaar, C.; Holt, M.; Cox, S.; Fountain, S.; Shanahan, C.; Warren, D. SUN1/2 Are Essential for RhoA/ROCK-Regulated Actomyosin Activity in Isolated Vascular Smooth Muscle Cells. Cells 2020, 9, 132.

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