Cavin‐3 deficiency reduces caveolae abundance in vascular and urinary bladder smooth muscle cells

Abstract

We investigated the effect of cavin‐3 (protein kinase C delta binding protein, Prkcdbp) deficiency on vascular and urinary bladder function. Small mesenteric arteries and the urinary bladder were isolated from mice lacking cavin‐3 (Prkcdbp−/−, knockout: KO) and from control littermates (Prkcdbp+/+, wild type: WT). One group of mice was used for blood pressure measurements, whereas another set of mice underwent bladder outlet obstruction followed by analysis of protein expression using western blotting. Our studies revealed that loss of cavin‐3 resulted in a 40% reduction of the caveola protein cavin‐1 (polymerase I and transcript release factor, Ptrf) in vascular and bladder smooth muscle. Electron microscopy demonstrated that loss of cavin‐3 was accompanied by a reduction of caveolae by 40% in smooth muscle, while the abundance of caveolae in endothelial cells was unchanged. Vascular contraction in response to cirazoline (α1‐adrenergic agonist) was normal, but nitric‐oxide dependent relaxation was enhanced. The latter effect was associated with elevated expression of soluble guanylyl cyclase, and yet blood pressure was similar in WT and KO mice. Contraction of the urinary bladder was not affected by loss of cavin‐3, and the proteomic response to outlet obstruction, including STAT3 (signal transducer and activator of transcription 3) phosphorylation, induction of synthetic markers, and repression of contractile markers were identical, the only exception being a curtailed induction of the Golgi protein GM130 (Golgi matrix protein 130 kD). In conclusion, 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 a somewhat disturbed Golgi homeostasis in a situation of severe cellular stress.Support or Funding InformationThis study was funded by The Swedish Research Council (Vetenskapsrådet, http://www.vr.se/, K2015‐65X‐22662‐01‐3/KS), the Crafoord Foundation (http://en.crafoord.se/, CR), and the Royal Physiographic Society (Kungliga Fysiografiska Sällskapet, http://www.fysiografen.se/, CR).