Faculty Collaboration Database

Protein methylation activates reconstituted ryanodine receptor-ca release channels from coronary artery myocytes. J Vasc Res 2004;41(3):229-40

Date

05/01/2004

Pubmed ID

15118362

DOI

10.1159/000078178

Scopus ID

2-s2.0-2942748235 (requires institutional sign-in at Scopus site)   20 Citations

Abstract

Ryanodine receptors (RyR) play an important role in the regulation of intracellular Ca(2+) concentration and in the control of vascular tone. However, the mechanism regulating the activity of RyR is poorly understood. The present study determined whether protein methylation participates in the control of RyR activity. Using a planar lipid bilayer clamping system, S-adenosyl-L-methionine (SAM), a methyl donor, significantly increased the activity of a 245-pS reconstituted Ca(2+) release channel from coronary arterial smooth muscle (CASM) in a concentration-dependent manner. Addition of the protein methylation blockers, 3-deazaadenosine, S-adenosylhomocysteine or sinefungin into the cis solution markedly attenuated SAM-induced activation of RyR/Ca(2+) release channels. By Western blot analysis, arginine N-methyltransferase (PRMT1) and FK506 binding protein (FKBP) were detected in the SR used for reconstitution of RyR. In the presence of anti-PRMT1 antibody (1:100), SAM-induced activation of RyR/Ca(2+) channel was completely abolished. In addition, this SAM-induced increase in RyR/Ca(2+) channel activity was blocked by 30 microM ryanodine and by FK506 (100 microM), a ligand for the RyR accessory protein. These results suggest that protein methylation activates RyR/Ca(2+) release channels and may participate in the control of intracellular Ca(2+) mobilization in CASM cells by transferring a methyl group to the arginine moiety of the RyR accessory protein, FKBP 12.

Author List

Chen YF, Zhang AY, Zou AP, Campbell WB, Li PL

Author

William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenosine
Animals
Antibodies
Arteries
Cattle
Coronary Vessels
Methylation
Muscle, Smooth, Vascular
Myocytes, Smooth Muscle
Protein-Arginine N-Methyltransferases
Ryanodine
Ryanodine Receptor Calcium Release Channel
S-Adenosylmethionine
Sarcoplasmic Reticulum
Tacrolimus
Tacrolimus Binding Protein 1A
Tubercidin