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Myocardin Family Members Drive Formation of Caveolae.

Krawczyk KK, Yao Mattisson I, Ekman M, Oskolkov N, Grantinge R, Kotowska D, Olde B, Hansson O, Albinsson S, Miano JM, Rippe C, Swärd K - PLoS ONE (2015)

Bottom Line: 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.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.The myocardin family of transcriptional coactivators therefore drives formation of caveolae and this effect is largely independent of SRF.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medical Science, BMC D12, Lund University, Lund, Sweden.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Chromatin remodeling plays role for the effects of myocardin family proteins on caveolin and cavin expression.Panels A and B show correlations between mRNAs for one component of the SWI/SNF chromatin remodeling complex (SMARCA2) and PTRF in tibial artery and colon, respectively. Panels C and D shows effect of adenoviral overexpression of SMARCA2 (hBrm) on CAV1 and PTRF, respectively, in human coronary artery smooth muscle cells.
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pone.0133931.g009: Chromatin remodeling plays role for the effects of myocardin family proteins on caveolin and cavin expression.Panels A and B show correlations between mRNAs for one component of the SWI/SNF chromatin remodeling complex (SMARCA2) and PTRF in tibial artery and colon, respectively. Panels C and D shows effect of adenoviral overexpression of SMARCA2 (hBrm) on CAV1 and PTRF, respectively, in human coronary artery smooth muscle cells.

Mentions: Prior work has demonstrated that myocardin family proteins recruit a SWI/SNF chromatin remodeling complex to SRF target genes and that this is important for their regulation. In keeping with this possibility we found that SMARCA2 (Brm) correlated with PTRF in tibial artery and colon in the GTEx database (Fig 9A and 9B). To support a cause and effect relationship experimentally we overexpressed SMARCA2 (Brm), both alone and together with MYOCD. No effect was seen on CAV1 (Fig 9C). For PTRF, on the other hand, we found significant transcriptional activation and an additive effect with MYOCD (Fig 9D).


Myocardin Family Members Drive Formation of Caveolae.

Krawczyk KK, Yao Mattisson I, Ekman M, Oskolkov N, Grantinge R, Kotowska D, Olde B, Hansson O, Albinsson S, Miano JM, Rippe C, Swärd K - PLoS ONE (2015)

Chromatin remodeling plays role for the effects of myocardin family proteins on caveolin and cavin expression.Panels A and B show correlations between mRNAs for one component of the SWI/SNF chromatin remodeling complex (SMARCA2) and PTRF in tibial artery and colon, respectively. Panels C and D shows effect of adenoviral overexpression of SMARCA2 (hBrm) on CAV1 and PTRF, respectively, in human coronary artery smooth muscle cells.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526231&req=5

pone.0133931.g009: Chromatin remodeling plays role for the effects of myocardin family proteins on caveolin and cavin expression.Panels A and B show correlations between mRNAs for one component of the SWI/SNF chromatin remodeling complex (SMARCA2) and PTRF in tibial artery and colon, respectively. Panels C and D shows effect of adenoviral overexpression of SMARCA2 (hBrm) on CAV1 and PTRF, respectively, in human coronary artery smooth muscle cells.
Mentions: Prior work has demonstrated that myocardin family proteins recruit a SWI/SNF chromatin remodeling complex to SRF target genes and that this is important for their regulation. In keeping with this possibility we found that SMARCA2 (Brm) correlated with PTRF in tibial artery and colon in the GTEx database (Fig 9A and 9B). To support a cause and effect relationship experimentally we overexpressed SMARCA2 (Brm), both alone and together with MYOCD. No effect was seen on CAV1 (Fig 9C). For PTRF, on the other hand, we found significant transcriptional activation and an additive effect with MYOCD (Fig 9D).

Bottom Line: 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.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.The myocardin family of transcriptional coactivators therefore drives formation of caveolae and this effect is largely independent of SRF.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medical Science, BMC D12, Lund University, Lund, Sweden.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus