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Cavin-3 (PRKCDBP) deficiency reduces the density of caveolae in smooth muscle

Zhu, Baoyi LU ; Swärd, Karl LU ; Ekman, Mari LU ; Uvelius, Bengt LU and Rippe, Catarina LU (2017) In Cell and Tissue Research1974-01-01+01:00 368(3). p.591-602
Abstract

Cavins belong to a family of proteins that contribute to the formation of caveolae, which are membrane organelles with functional roles in muscle and fat. Here, we investigate the effect of cavin-3 ablation on vascular and urinary bladder structure and function. Arteries and urinary bladders from mice lacking cavin-3 (knockout: KO) and from controls (wild type: WT) were examined. Our studies revealed that the loss of cavin-3 resulted in ∼40% reduction of the caveolae protein cavin-1 in vascular and bladder smooth muscle. Electron microscopy demonstrated that the loss of cavin-3 was accompanied by a reduction of caveolae abundance by 40-45% in smooth muscle, whereas the density of caveolae in endothelial cells was unchanged. Vascular... (More)

Cavins belong to a family of proteins that contribute to the formation of caveolae, which are membrane organelles with functional roles in muscle and fat. Here, we investigate the effect of cavin-3 ablation on vascular and urinary bladder structure and function. Arteries and urinary bladders from mice lacking cavin-3 (knockout: KO) and from controls (wild type: WT) were examined. Our studies revealed that the loss of cavin-3 resulted in ∼40% reduction of the caveolae protein cavin-1 in vascular and bladder smooth muscle. Electron microscopy demonstrated that the loss of cavin-3 was accompanied by a reduction of caveolae abundance by 40-45% in smooth muscle, whereas the density of caveolae in endothelial cells was unchanged. Vascular contraction in response to an α1-adrenergic agonist was normal but nitric-oxide-dependent relaxation was enhanced, in parallel with an increased relaxation on direct activation of soluble guanylyl cyclase (sGC). This was associated with an elevated expression of sGC, although blood pressure was similar in WT and KO mice. Contraction of the urinary bladder was not affected by the loss of cavin-3. The proteomic response to outlet obstruction, including STAT3 phosphorylation, the induction of synthetic markers and the repression of contractile markers were identical in WT and KO mice, the only exception being a curtailed induction of the Golgi protein GM130. Loss of cavin-3 thus reduces the number of caveolae in smooth muscle and partly destabilizes cavin-1 but the functional consequences are modest and include an elevated vascular sensitivity to nitric oxide and slightly disturbed Golgi homeostasis in situations of severe cellular stress.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Caveolin-1, Cavin-1, Detrusor, Vascular function
in
Cell and Tissue Research1974-01-01+01:00
volume
368
issue
3
pages
591 - 602
publisher
Springer
external identifiers
  • scopus:85014969613
  • wos:000401328400013
ISSN
0302-766X
DOI
10.1007/s00441-017-2587-y
language
English
LU publication?
yes
id
364f9c3e-a101-48eb-bf5b-ea6e0c163acd
date added to LUP
2017-04-03 11:14:58
date last changed
2018-01-07 11:57:42
@article{364f9c3e-a101-48eb-bf5b-ea6e0c163acd,
  abstract     = {<p>Cavins belong to a family of proteins that contribute to the formation of caveolae, which are membrane organelles with functional roles in muscle and fat. Here, we investigate the effect of cavin-3 ablation on vascular and urinary bladder structure and function. Arteries and urinary bladders from mice lacking cavin-3 (knockout: KO) and from controls (wild type: WT) were examined. Our studies revealed that the loss of cavin-3 resulted in ∼40% reduction of the caveolae protein cavin-1 in vascular and bladder smooth muscle. Electron microscopy demonstrated that the loss of cavin-3 was accompanied by a reduction of caveolae abundance by 40-45% in smooth muscle, whereas the density of caveolae in endothelial cells was unchanged. Vascular contraction in response to an α<sub>1</sub>-adrenergic agonist was normal but nitric-oxide-dependent relaxation was enhanced, in parallel with an increased relaxation on direct activation of soluble guanylyl cyclase (sGC). This was associated with an elevated expression of sGC, although blood pressure was similar in WT and KO mice. Contraction of the urinary bladder was not affected by the loss of cavin-3. The proteomic response to outlet obstruction, including STAT3 phosphorylation, the induction of synthetic markers and the repression of contractile markers were identical in WT and KO mice, the only exception being a curtailed induction of the Golgi protein GM130. Loss of cavin-3 thus reduces the number of caveolae in smooth muscle and partly destabilizes cavin-1 but the functional consequences are modest and include an elevated vascular sensitivity to nitric oxide and slightly disturbed Golgi homeostasis in situations of severe cellular stress.</p>},
  author       = {Zhu, Baoyi and Swärd, Karl and Ekman, Mari and Uvelius, Bengt and Rippe, Catarina},
  issn         = {0302-766X},
  keyword      = {Caveolin-1,Cavin-1,Detrusor,Vascular function},
  language     = {eng},
  month        = {03},
  number       = {3},
  pages        = {591--602},
  publisher    = {Springer},
  series       = {Cell and Tissue Research1974-01-01+01:00},
  title        = {Cavin-3 (PRKCDBP) deficiency reduces the density of caveolae in smooth muscle},
  url          = {http://dx.doi.org/10.1007/s00441-017-2587-y},
  volume       = {368},
  year         = {2017},
}