Abstract. Adult mouse brain contains at least two distinct spectrin subtypes, both consisting of 240-kD and 235-kD subunits. Brain spectrin(240/235) is found in neuronal axons, but not dendrites, when immunohistochemistry is performed with antibody raised against brain spectrin isolated from enriched synaptic/axonal membranes. A second spectrin subtype, brain spectrin(240/235E), is exclusively recognized by red blood cell spectrin antibody. Brain spectrin(240/235E) is confined to neuronal cell bodies and dendrites, and some glial cells, but is not present in axons or presynaptic terminals.

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...

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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.