Proteolipid protein mRNA stability is regulated by axonal contact in the rodent peripheral nervous system

Proteolipid protein (PLP) and its alternatively spliced isoform, DM20, are the main intrinsic membrane proteins of compact myelin in the CNS. PLP and DM20 are also expressed by Schwann cells, the myelin-forming cells in the P NS, and are necessary for normal PNS function in humans. We have investigat ed the expression of PLP in the PNS by examining transgenic mice expressing a LacZ transgene under the control of the PLP promoter. In these animals, myelinating Schwann cells expressed beta-galactosidase more prominently tha n nonmyelinating Schwann cells. PLP/DM20 mRNA levels, but not those of LacZ mRNA, increased during sciatic nerve development and decreased after axoto my, with resultant Wallerian degeneration. PLP/DM20 transcription rates, in nuclear run off experiments, however, did not increase in developing rat s ciatic nerve despite robust increases in PLP/DM20 mRNA levels during the sa me period. In RNAse protection studies, PLP mRNA levels fell to undetectabl e levels following nerve transection whereas levels of DM20 were essentiall y unchanged despite both being transcribed from the same promoter. Finally, cotransfection studies demonstrated that PLP-GFP, but not DM20-GFP mRNA is down-regulated in Schwann cells cultured in the absence of forskolin. Take n together these data demonstrate that steady state levels of PLP mRNA are regulated at a posttranscriptional level in Schwann cells, and that this re gulation is mediated by Schwann cell-axonal contact. Since the difference b etween these two mRNAs is a 105-bp sequence in PLP and not in DM20, this se quence is likely to play a role in the regulation of PLP mRNA. (C) 2000 Joh n Wiley & sons, Inc.