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Ola Hansson

Ola Hansson

Principal investigator

Ola Hansson

Myocardin Family Members Drive Formation of Caveolae.

Author

  • Katarzyna Krawczyk
  • Ingrid Yao Mattisson
  • Mari Ekman
  • Nikolay Oskolkov
  • Rebecka Grantinge
  • Dorota Kotowska
  • Björn Olde
  • Ola Hansson
  • Sebastian Albinsson
  • Joseph M Miano
  • Catarina Rippe
  • Karl Swärd

Summary, in English

Caveolae are membrane organelles that play roles in glucose and lipid metabolism and in vascular function. Formation of caveolae requires caveolins and cavins. The make-up of caveolae and their density is considered to reflect cell-specific transcriptional control mechanisms for caveolins and cavins, but knowledge regarding regulation of caveolae genes is incomplete. Myocardin (MYOCD) and its relative MRTF-A (MKL1) are transcriptional coactivators that control genes which promote smooth muscle differentiation. MRTF-A communicates changes in actin polymerization to nuclear gene transcription. Here we tested if myocardin family proteins control biogenesis of caveolae via activation of caveolin and cavin transcription. Using human coronary artery smooth muscle cells we found that jasplakinolide and latrunculin B (LatB), substances that promote and inhibit actin polymerization, increased and decreased protein levels of caveolins and cavins, respectively. The effect of LatB was associated with reduced mRNA levels for these genes and this was replicated by the MRTF inhibitor CCG-1423 which was non-additive with LatB. Overexpression of myocardin and MRTF-A caused 5-10-fold induction of caveolins whereas cavin-1 and cavin-2 were induced 2-3-fold. PACSIN2 also increased, establishing positive regulation of caveolae genes from three families. Full regulation of CAV1 was retained in its proximal promoter. Knock down of the serum response factor (SRF), which mediates many of the effects of myocardin, decreased cavin-1 but increased caveolin-1 and -2 mRNAs. Viral transduction of myocardin increased the density of caveolae 5-fold in vitro. A decrease of CAV1 was observed concomitant with a decrease of the smooth muscle marker calponin in aortic aneurysms from mice (C57Bl/6) infused with angiotensin II. Human expression data disclosed correlations of MYOCD with CAV1 in a majority of human tissues and in the heart, correlation with MKL2 (MRTF-B) was observed. The myocardin family of transcriptional coactivators therefore drives formation of caveolae and this effect is largely independent of SRF.

Department/s

  • Cellular Biomechanics
  • Cardiovascular Research - Immunity and Atherosclerosis
  • Molecular Vascular Physiology
  • Genomics, Diabetes and Endocrinology
  • Glucose Transport and Protein Trafficking
  • Cardiology
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year

2015

Language

English

Publication/Series

PLoS ONE

Volume

10

Issue

8

Document type

Journal article

Publisher

Public Library of Science

Topic

  • Cardiac and Cardiovascular Systems

Status

Published

Research group

  • Cellular Biomechanics
  • Cardiovascular Research - Immunity and Atherosclerosis
  • Molecular Vascular Physiology
  • Genomics, Diabetes and Endocrinology
  • Glucose Transport and Protein Trafficking

ISBN/ISSN/Other

  • ISSN: 1932-6203