Isoprenylated proteins in myelin.
Incubation of rat brainstem slices with [3H]-mevalonate ([3H]MVA) in the presence of lovastatin resulted in the incorporation of label into three groups of myelin-associated proteins with molecular masses of 47, 21-27, and 8 kDa, as revealed on sodium dodecyl sulfate-polyacrylamide rod gel electrophoresis. Although the gel patterns of [3H]MVA-derived prenylated proteins were similar, the relative level of 3H incorporated into each protein species differed between myelin and the brainstem homogenate. Immunoprecipitation studies identified the 47-kDa prenylated protein as a 2'-3'-cyclic nucleotide phosphodiesterase, whereas the 8-kDa protein proved to be the gamma subunit of membrane-associated guanine nucleotide regulatory protein. The 3H-labeled 21-27-kDa group in myelin corresponds to the molecular mass of the extensive Ras-like family of monomeric GTP-binding proteins known to be prenylated in other tissues. Increase in lovastatin concentration resulted in reduced levels of [3H]MVA-labeled species in myelin and concomitantly increased levels in the cytosol. A cold MVA chase restored to normality the appearance of [3H]MVA-labeled proteins in myelin. Furthermore, a high lovastatin concentration in the brainstem slice incubation mixture altered the appearance of newly synthesized nonprenylated myelin proteins, including proteolipid protein and the 17-kDa subspecies of myelin basic protein. Because other myelin proteins were unaffected by the high lovastatin concentration, restricting the availability of MVA in myelin-forming cells may selectively alter processes required for myelinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Sepp-Lorenzino
L
L
SKI Program in Cell Biology, Memorial Sloan-Kettering Cancer Center, New York, New York.
Coleman
P S
PS
Larocca
J N
JN
D000818:Animals; D001933:Brain Stem / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007163:Immunosorbent Techniques; D008148:Lovastatin / Q000494:pharmacology; D008798:Mevalonic Acid / Q000378:metabolism*; D009185:Myelin Proteins / Q000378:metabolism*; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism*; D017368:Protein Prenylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009185:Myelin Proteins; D014316:Tritium; D008148:Lovastatin; D006903:Hydroxymethylglutaryl CoA Reductases; D019204:GTP-Binding Proteins; D008798:Mevalonic Acid