Journal of Neuroscience, Vol 7, 55-64, Copyright © 1987 by Society for Neuroscience
Ontogeny, compartmentation, and turnover of spectrin isoforms in rat central neurons
R Siman, M Ahdoot and G Lynch
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.
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