M. Yamada et al., Proteolipid protein gene product can be secreted and exhibit biological activity during early development, J NEUROSC, 19(6), 1999, pp. 2143-2151
A gene encoding myelin proteolipid protein (PLP) and its smaller isoform DM
20 is expressed at least 1 week before myelination. Mutations within the ge
ne cause abnormalities in the development of premyelinating oligodendrocyte
s, resulting in hypomyelinating disorders. These findings suggest a premyel
inating 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 i
s mediated by a secreted fragment containing the G-terminal portion of PLP.
This factor increased the bromodeoxyuridine incorporation rate in both oli
godendrocyte 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 s
ecreted PLP gene product exerts biological activity at a premyelinating sta
ge before the major induction of the gene.