GABA-modulin: a synaptosomal basic protein that differs from small myelin basic protein of rat brain.
GABA-modulin, a basic protein that allosterically inhibits the high-affinity binding of GABA to its recognition sites, has been extracted and purified from the synaptosomal fraction of rat brain where it represents approximately 0.5% of the total synaptosomal proteins. GABA-modulin has characteristics in common to the class of highly basic proteins isolated from myelin, in particular to the rat small myelin basic protein (SMBP). However, GABA-modulin is located selectively in synaptosomes, whereas the SMBP is located in myelin. Moreover, synaptosomal GABA-modulin is different from SMBP in amino acid composition (it contains more Glx and Lys and fewer Arg residues) and in apparent molecular weight (17,000 and 15,000 for GABA-modulin and SMBP, respectively). Synaptosomal GABA-modulin fails to bind [3H]muscimol per se but noncompetitively inhibits (IC30 approximately 0.5 microM) the binding of [3H]muscimol to purified synaptic membranes. Cyanogen bromide treatment generated a 13,000 MW major fragment from both SMBP and GABA-modulin. These two fragments were compared and showed differences in amino acid composition and sequence. Moreover, the peptide maps generated from GABA-modulin and SMBP by trypsin and staphylococcal V8 protease digestion are different. The high concentration of GABA-modulin in synaptosomal membranes, its high potency in the inhibition of GABA binding, and its neuronal specificity suggest that GABA-modulin plays an important role in neuronal membrane function linked to the modulation of GABA and perhaps other neurotransmitter receptors.
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001923:Brain Chemistry; D002352:Carrier Proteins; D002851:Chromatography, High Pressure Liquid; D003488:Cyanogen Bromide / Q000494:pharmacology; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009118:Muscimol / Q000378:metabolism; D009185:Myelin Proteins / Q000032:analysis*; D009186:Myelin Sheath / Q000032:analysis; D009419:Nerve Tissue Proteins / Q000032:analysis*; D027361:Organic Anion Transporters; D010446:Peptide Fragments / Q000032:analysis; D051381:Rats; D013347:Subcellular Fractions / Q000032:analysis; D013574:Synaptosomes / Q000032:analysis; D014018:Tissue Distribution
D000596:Amino Acids; D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D027361:Organic Anion Transporters; D010446:Peptide Fragments; D009118:Muscimol; D003488:Cyanogen Bromide