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The Journal of Neuroscience, March 15, 1999, 19(6):2143-2151

Proteolipid Protein Gene Product Can Be Secreted and Exhibit Biological Activity during Early Development

Masahisa Yamada¹, Anna Ivanova¹, Yoshihide Yamaguchi¹, Marjorie B. Lees², and Kazuhiro Ikenaka¹

¹ Laboratory of Neural Information, National Institute for Physiological Sciences, Okazaki National Research Institutes, Aichi 444-8585, Japan, and ² Biochemistry Division, E. K. Shriver Center, Waltham, Massachusetts 02254

A gene encoding myelin proteolipid protein (PLP) and its smaller isoform DM20 is expressed at least 1 week before myelination. Mutations within the gene cause abnormalities in the development of premyelinating oligodendrocytes, resulting in hypomyelinating disorders. These findings suggest a premyelinating function of the PLP gene products. We previously demonstrated that PLP gene expression is directly associated with secretion of a factor that increases the number of oligodendrocytes. Here we show that this activity is mediated by a secreted fragment containing the C-terminal portion of PLP. This factor increased the bromodeoxyuridine incorporation rate in both oligodendrocyte and astrocyte lineage cells; a synthetic peptide (PLP 215-232) exhibited a similar activity. Dose-response curves of PLP and PLP peptide showed maximum activities at a concentration in the picomolar range, which decreased at higher concentrations. These observations demonstrate that a secreted PLP gene product exerts biological activity at a premyelinating stage before the major induction of the gene.

Key words: oligodendrocyte development; myelin proteolipid protein; DM20; differentiation factor; myelin; cell culture

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Copyright © 1999 Society for Neuroscience  0270-6474/99/1962143-09$05.00/0

This article has been cited by other articles:

				S. E. M. Boucher, M. A. Cypher, L. R. Carlock, and R. P. Skoff Proteolipid Protein Gene Modulates Viability and Phenotype of Neurons J. Neurosci., March 1, 2002; 22(5): 1772 - 1783. [Abstract] [Full Text] [PDF]

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