ADHESIVE PROPERTIES OF PROTEOLIPID PROTEIN ARE RESPONSIBLE FOR THE COMPACTION OF CNS MYELIN SHEATHS

We have studied the molecular function of proteolipid protein (PLP), t he main integral membrane protein of CNS myelin, by generating mice la cking PLP expression. Here, we demonstrate that these PLP-minus mice s how no pleiotropism as mice carrying point mutations within the PLP ge ne. The expression of other myelin genes (myelin basic protein, MBP; m yelin associated glycoprotein, MAG; UDP-galactose-ceramide galactosyl transferase, CGT) is unimpaired on the RNA level. Protein level immuno fluorescence analysis by confocal microscopy reveals that in PLP-minus mice there is a complete absence of PLP, a scattered appearance of MB P, and MAG expressed more widely in regions lacking MBP staining, whic h may be a compensatory mechanism. In electron microscopy the myelin l amellae of the ensheathed CNS axons are loosely wrapped with wide extr acellular spaces between turning loops. Intraperiod dense lines are mi ssing. The lateral loops of the paranode form regular axoglial junctio ns. In PLP-minus mice axons with large diameters are loosely myelinate d, whereas small axons remain unmyelinated. Functionally, the mutant m ice show deficits in their locomotor activity. We propose that adhesio n properties of the extracellular domains of PLP are responsible for t he tight apposition of the plasma membrane processes of oligodendrocyt es wrapping axons to form the compact myelin sheath.