A novel isoform of beta-spectrin II localizes to cerebellar Purkinje-cell bodies and interacts with neurofibromatosis type 2 gene product schwannomin

We report the identification of a full-length novel beta -spectrin II gene (beta SpII Sigma2) in human brain. The beta SpII Sigma2 gene has 32 exons e ncoding an actin-binding domain, followed by 17-spectrin repeats, and a sho rt COOH-terminal regulatory region that lacks the Pleckstrin homology (PH) domain. Pair-wise sequence analysis showed an additional 36 and 28 amino ac ids located at the NH2 and COOH-terminal regions of beta SpII Sigma2, respe ctively. Northern-blot analysis showed an abundant expression of beta SpII Sigma2 transcripts in brain, lung, and kidney. Western-blot analysis confir med the predicted similar to 225 kD molecular size of beta SpII Sigma2 prot ein in these same tissues. In brain, immunofluorescent staining revealed th at beta SPII Sigma2 was enriched in cerebellar neurons, with specific enric hment in Purkinje cell bodies, but not in dendrites. Of considerable intere st, neurofibromatosis type 2 (NF2) gene product schwannomin was found to co -immunoprecipitate with beta SpII Sigma2 in cultured Purkinje cells. These results suggest that beta SpII Sigma2 may play an important role in the ass embly of the specialized plasma membrane domain of Purkinje neurons and tha t schwannomin may be involved in actin-cytoskeleton organization by interac ting with beta SpII Sigma2.