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GABA‐Modulin: A Synaptosomal Basic Protein that Differs from Small Myelin Basic Protein of Rat Brain
Author(s) -
Vaccarino Flora,
Tronconi Bianca M. Conti,
Panula Pertti,
Guidotti Alessandro,
Costa Erminio
Publication year - 1985
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1985.tb07142.x
Subject(s) - chemistry , biochemistry , myelin , cyanogen bromide , synaptic membrane , membrane , central nervous system , peptide sequence , biology , endocrinology , gene
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 [ 3 H]muscimol per se but noncompetitively inhibits (IC 50 ˜ 0.5 μ M ) the binding of [ 3 H]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.