Adhesive properties of proteolipid protein are responsible for the compaction of CNS myelin sheaths.

ABSTRACT

We have studied the molecular function of proteolipid protein (PLP), the main integral membrane protein of CNS myelin, by generating mice lacking PLP expression. Here, we demonstrate that these PLP-minus mice show no pleiotropism as mice carrying point mutations within the PLP gene. The expression of other myelin genes (myelin basic protein, MBP; myelin associated glycoprotein, MAG; UDP-galactose-ceramide galactosyl transferase, CGT) is unimpaired on the RNA level. Protein level immunofluorescence analysis by confocal microscopy reveals that in PLP-minus mice there is a complete absence of PLP, a scattered appearance of MBP, and MAG expressed more widely in regions lacking MBP staining, which may be a compensatory mechanism. In electron microscopy the myelin lamellae of the ensheathed CNS axons are loosely wrapped with wide extracellular spaces between turning loops. Intraperiod dense lines are missing. The lateral loops of the paranode form regular axoglial junctions. In PLP-minus mice axons form regular axoglial junctions. In PLP-minus mice axons with large diameters are loosely myelinated, whereas small axons remain unmyelinated. Functionally, the mutant mice show deficits in their locomotor activity. We propose that adhesion properties of the extracellular domains of PLP are responsible for the tight apposition of the plasma membrane processes of oligodendrocytes wrapping axons to form the compact myelin sheath.