title: Protein methylation inhibits Na+-Ca2+ exchange activity in cardiac sarcolemmal vesicles.
abstract: We have examined the effect of membrane methylation on the Na+-Ca2+ exchange activity of canine cardiac sarcolemmal vesicles using S-adenosyl-L-methionine as methyl donor. Methylation leads to approximately 40% inhibition of the initial rate of Nai+-dependent Ca2+ uptake. The inhibition is due to a lowering of the Vmax for the reaction. The inhibition is not due to an effect on membrane permeability and is blocked by S-adenosyl-L-homocysteine, an inhibitor of methylation reactions. The following experiments indicated that inhibition of Na+-Ca2+ exchange was due to methylation of membrane protein and not due to methylated phosphatidylethanolamine (PE) compounds (i.e., phosphatidyl-N-monomethylethanolamine (PMME) or phosphatidyl-N,N'-dimethylethanolamine (PDME]: (1) We solubilized sarcolemma and reconstituted activity into vesicles containing no PE. The inhibition by S-adenosyl-L-methionine was not diminished in this environment. (2) We reconstituted sarcolemma into vesicles containing PMME or PDME. These methylated lipid components had no effect on Na+-Ca2+ exchange activity. (3) We verified that many membrane proteins, probably including the exchanger, become methylated.
authors: Department of Medicine, University of California, Los Angeles, School of Medicine 90024-1760.
authors: R
authors: R
authors: Vemuri
authors: K D
authors: KD
authors: Philipson
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002458:Cell Fractionation; D002784:Cholesterol; D004285:Dogs; D007700:Kinetics; D008081:Liposomes; D008745:Methylation; D009206:Myocardium / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000378:metabolism / Q000494:pharmacology; D012508:Sarcolemma / Q000378:metabolism* / Q000648:ultrastructure; D019831:Sodium-Calcium Exchanger
chemical_list: D002352:Carrier Proteins; D008081:Liposomes; D019831:Sodium-Calcium Exchanger; D012436:S-Adenosylmethionine; D002784:Cholesterol; D002118:Calcium