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© The Rockefeller University Press,
0021-9525/2000//985 $5.00
The Journal of Cell Biology, Volume 151, Number 5,
, 2000 985-1002
Original Article |
βiv Spectrin, a New Spectrin Localized at Axon Initial Segments and Nodes of Ranvier in the Central and Peripheral Nervous System
We report the identification of βIV spectrin, a novel spectrin isolated as an interactor of the receptor tyrosine phosphatase-like protein ICA512. The βIV spectrin gene is located on human and mouse chromosomes 19q13.13 and 7b2, respectively. Alternative splicing of βIV spectrin generates at least four distinct isoforms, numbered βIV
1–βIV4 spectrin. The longest isoform (βIV1 spectrin) includes an actin-binding domain, followed by 17 spectrin repeats, a specific domain in which the amino acid sequence ERQES is repeated four times, several putative SH3-binding sites and a pleckstrin homology domain. βIV2 and βIV3 spectrin encompass the NH2- and COOH-terminal halves of βIV1 spectrin, respectively, while βIV4 spectrin lacks the ERQES and the pleckstrin homology domain. Northern blots revealed an abundant expression of βIV spectrin transcripts in brain and pancreatic islets. By immunoblotting, βIV1 spectrin is recognized as a protein of 250 kD. Anti–βIV spectrin antibodies also react with two additional isoforms of 160 and 140 kD. These isoforms differ from βIV1 spectrin in terms of their distribution on subcellular fractionation, detergent extractability, and phosphorylation. In islets, the immunoreactivity for βIV spectrin is more prominent in 
than in β cells. In brain, βIV spectrin is enriched in myelinated neurons, where it colocalizes with ankyrinG 480/270-kD at axon initial segments and nodes of Ranvier. Likewise, βIV spectrin is concentrated at the nodes of Ranvier in the rat sciatic nerve. In the rat hippocampus, βIV1 spectrin is detectable from embryonic day 19, concomitantly with the appearance of immunoreactivity at the initial segments. Thus, we suggest that βIV1 spectrin interacts with ankyrinG 480/270-kD and participates in the clustering of voltage-gated Na+ channels and cell-adhesion molecules at initial segments and nodes of Ranvier.
Key Words: chromosome 19 • diabetes • neuropathies • secretion • signal transduction
© 2000 The Rockefeller University Press
Portions of this work were previously published in abstract form (Berghs, S., D. Aggujaro, R. Dirkx, J.-P. Zhang, and M. Solimena. 1998. Soc. Neurosci. 24:204–210).Abbreviations used in this paper: 3-AT, 3-amino-1,2,4-triazole; CT, COOH-terminal domain antiserum; HA, hemagglutinin; HB, homogenization buffer; HSP, high-speed pellet; HSS, high-speed supernatant; PH, pleckstrin homology; PNS, post-nuclear supernatant; PTP, protein tyrosine phosphatase; SD, specific domain antiserum.
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