Spectrin is a major cytoskeletal component of the brain. At least 2 distinct spectrin subtypes are found in mammalian brain: brain spectrin(240/235) and brain spectrin(240/235E). In the present study spectrin subtypes were localized in the adult mouse brain by immunoelectron microscopy using antibodies that recognize each subtype. Brain spectrin (240/235E) was concentrated in neuronal cell bodies, dendrites, and postsynaptic terminals. It was also prominently associated with the plasma membrane, microtubules, filaments, mitochondria, endoplasmic reticulum, and nuclear envelope, and it appeared to interconnect structural elements within the cell. Brain spectrin(240/235E) also was localized to the plasma membrane, nuclear envelope, and cytoplasmic organelles of glial cell bodies. Brain spectrin(240/235) was detected in axons and presynaptic elements, where it was associated with the plasma membrane, microtubules, filaments, synaptic vesicles, and mitochondria. These results show that (1) spectrin is distributed throughout the cytoplasm of neural cells, (2) the location of spectrin is dependent on subtype, and (3) the cytoplasmic surface of plasma membrane and organelles contains an extensive and intricate spectrin meshwork.Brain spectrin is an analog of erythrocyte spectrin, which, like its erythrocyte counterpart, is an elongated fibrous protein of 2000 8, contour length, with a molecular weight of 1 x lo6 Da and an (c@)* tetrameric subunit composition (for review, see Zagon, 1984, 1986). The a-subunits of brain and red blood cell (rbc) spectrin have an apparent molecular weight of 240 kDa, while the p-subunits are 235 kDa (brain) and 220 kDa (rbc). Other similarities between brain and rbc spectrin include binding sites for actin at the terminal ends of the molecule (Glenney et al., 1982) a binding site for brain ankyrin 800 A from the end of the p-subunit (Davis and Bennett, 1984) a binding site for brain protein 4.1 at the ends of the molecule (Goodman and Zagon, 1986) and a phosphorylated P-subunit (Goodman et al., 1983). In the case of mammalian brain spectrin, both the 01-and P-subunits are distinct gene products from rbc spectrin 01-and P-subunits (for reviews, see Zagon, 1984, 1986).Fodrin, a molecule we now know to be equivalent to brain spectrin, has been localized to the cortical cytoplasm of guinea pig neuronal cell bodies, axons, and dendrites, as well as Schwann cells (Levine and Willard, 198 l), using an antibody directed against the 24@ kDa a-subunit of brain spectrin . Zagon et al. (1984) using an antibody against mouse rbc spectrin, which detected 240 and 235 kDa polypeptides exclu- Received Nov. 21, 1985; revised Jan. 27, 1986; accepted Mar. 28, 1986. This work was supported in part by NIH Grants NS-21246, NS-20623, and NS-20500 (I.S.Z.), and Grants NS-19357 and HL-26059 (S.R.G. sively on immunoautoradiography of total mouse brain protein, localized brain spectrin to neuronal cell bodies and dendrites, but not axons. Staining of glial cell bodies with rbc spectrin antibody was also obser...

The discovery of nonerythroid spectrin (Goodman et al., Proc. Natl. Acad. Sci. USA 78: 7570-7574, 1981) has generated interest equivalent to that occurring upon the identification of nonmuscle actin and myosin. Brain spectrin has become the best-studied member of the nonerythroid spectrin family of molecules. In this review, we discuss the structure and functional interactions of brain spectrin, as a prelude to attempting to resolve what are some of the more controversial questions in the field. We finish with a discussion of what may be the most profitable directions for future research.

Mouse brain contains at least 2 distinct spectrin subtypes: brain spectrin(240/235) and brain spectrin(240/235E) (Riederer et al., 1986). In this study, we demonstrate that these subtypes are differentially expressed during mouse brain development. Brain spectrin(240/235) can be detected in fetal tissue and increases 2-fold during brain development. This subtype is enriched in the cortical cytoplasm of germinative neural cells and is also found in fibers resembling axons as early as fetal life. Brain spectrin(240/235E), which is specifically detected with antibodies to red blood cell spectrin, is below the limits of detection in fetal and neonatal brain but rapidly increases in concentration during the second postnatal week. Brain spectrin(240/235E) is confined to the cell body and dendrites of differentiating neurons and to glial cells but is not expressed in mitotic cells. This subtype is most prominent in granule cells of the cerebellum and dentate gyrus in the hippocampus.

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Spectrin is a major skeletal component of the erythrocyte membrane and is essential in controlling cell shape and structural stability. The brain has also been found to be rich in an immunoreactive and structural analogue of spectrin. In the present study, spectrin was localized in the mouse brain by indirect immunofluorescence using an antibody to erythrocyte spectrin that cross-reacts specifically with the alpha and beta subunits of brain spectrin. Spectrin antigens were concentrated in neuronal perikarya and cell processes. Synaptic structures and axons were observed to have little detectable spectrin antigen by immunofluorescence methodology. The cell bodies of glia had a less intense immunoreactivity in contrast to neurons, and glial processes and myelin were unstained. Cell nuclei of neural cells were not fluorescent. These results show that (a) spectrin is found in all regions of mammalian brain and its intensity corresponds to neural cell density, (b) different neural cell types contain variable spectrin content, and (c) within a single neural cell, the regional disposition of spectrin varies.