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Detection and processing of peripheral myelin protein PMP22 in cultured Schwann cells.

Peripheral myelin protein, 22 kDa ( PMP22), is a myelin molecule associated with Schwann cells in peripheral nerves (Snipes, G. J., Suter, U., Welcher, A. A., and Shooter, E. M. (1992) J. Cell Biol. 117, 225-238). Mutations affecting the PMP22 gene have been implicated in the trembler mutation in mice (Suter, U., Welcher, A. A., Ozcelik, T., Snipes, G. J., Kosaras, B., Francke, U., Billings-Gagliardi, S., Sidman, R. L., and Shooter, E. M. (1992) Nature 356, 241-244; Suter, U., Moskow, J. J., Welcher, A. A., Snipes, G. J., Kosaras, B., Sidman, R. L., Buchberg, A. M., and Shooter, E. M. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 4382-4386) and Charcot-Marie-Tooth Disease in humans (Patel, P. I., Roa, B. B., Welcher, A. A., Schoener-Scott, R., Trask, B. J., Pentao, L., Snipes, G. J., Garcia, C. A., Francke, U., Shooter, E. M., Lupski, J. R., and Suter, U. (1992) Nature genet. 1, 159-165). In this report, we have studied PMP22 production in cultured rat Schwann cells. Schwann cells contain a 1.8-kilobase mRNA transcript coding for PMP22, and its production is up-regulated in vitro by forskolin. Metabolic labeling combined with immunoprecipitation methods using antibodies raised against synthetic peptides of PMP22 reveal that Schwann cells generate the protein from an 18-kDa precursor form which is post-translationally modified by N-linked glycosylation. A second molecule (molecular mass, 48 kDa) that reacted with PMP22 antibodies was also detected in Schwann cells but is not related chemically to PMP22 as determined by pulse-chase labeling. Metabolic labeling of rat sciatic nerve and Western blot analyses of purified rat sciatic nerve myelin reveal that deglycosylation of PMP22 gives rise to an 18-kDa protein similar in size to that in Schwann cells. These results indicate that cultured Schwann cells may provide a good model in which to investigate the production and function of PMP22 and to establish the cellular basis for the protein's involvement in inherited peripheral neuropathies.[1]

References

  1. Detection and processing of peripheral myelin protein PMP22 in cultured Schwann cells. Pareek, S., Suter, U., Snipes, G.J., Welcher, A.A., Shooter, E.M., Murphy, R.A. J. Biol. Chem. (1993) [Pubmed]
 
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