Ontogeny, compartmentation, and turnover of spectrin isoforms in rat central neurons.
A variant of a principal structural protein of erythrocytes, spectrin, is a major neuronal protein. Here we have examined the subcellular and regional distributions, subunit composition, ontogeny, and metabolism of spectrin in rat CNS. While all subcellular fractions, except the mitochondrial, expressed the previously characterized brain form of spectrin (fodrin, or alpha gamma-spectrin), limited brain regions contained, in cytoplasm, a second isoform immunologically related to erythrocyte alpha beta-spectrin. Both alpha gamma- and alpha beta-spectrin are primarily neuronal, as evidenced by immunocytochemistry. The spectrins are distributed between 2 distinct subneuronal compartments: a membrane-associated domain containing alpha gamma-spectrin in relatively constant amounts across brain regions, and a cytoplasmic domain containing both the alpha gamma and alpha beta isoforms in widely varying amounts across brain regions. Although forebrain has considerable alpha beta-spectrin, the diencephalon, mesencephalon, and brain stem are devoid of this isoform. Further evidence for spectrin compartmentation comes from its ontogeny. Membrane-associated alpha gamma-spectrin is present at birth at its adult levels, but cytoplasmic alpha beta-spectrin is expressed only following the second postnatal week. Similarly, the 4-fold difference in cytoplasmic alpha gamma-spectrin content across brain regions develops during the third postnatal week. In this compartment, both spectrin forms may be metabolized in vivo, at least in part, by calcium-activated proteolysis. The presence in mammalian neurons of 2 spectrin isoforms and their compartmentation into distinct domains suggests multiple functions for neuronal spectrin, one of which may be in the stabilization or maturation of forebrain neurons.
D000375:Aging / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism; D005260:Female; D007424:Intracellular Fluid / Q000032:analysis; D008297:Male; D008970:Molecular Weight; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013049:Spectrin / Q000378:metabolism*; D013347:Subcellular Fractions / Q000032:analysis
D013049:Spectrin; D002154:Calpain