Ionic strength and calcium regulate the membrane interactions of myelin basic protein and the cytoplasmic domain of myelin protein zero

The formation of a mature myelin sheath in the vertebrate nervous system requires specific protein-membrane interactions. Several myelin-specific proteins are involved in the stacking of lipid membranes into multilayered structures around neuronal axons, and misregulation of these processes may contribute to chronic demyelinating diseases. Two key proteins functioning in myelin membrane binding and stacking are the myelin basic protein (MBP) and protein zero (P0). Other factors, including Ca2+, are important for the regulation of myelination. Here, we studied the effects of ionic strength and Ca2+ on the direct molecular membrane interactions of MBP and the cytoplasmic domain of P0 (P0ct). While both MBP and P0ct bound and aggregated negatively charged lipid vesicles, while simultaneously folding, both ionic strength and calcium had systematic effects on these interactions. Especially when decreasing membrane net negative charge, the level and kinetics of vesicle aggregation, which is a functional assay for myelin membrane-stacking proteins, were affected by both salt and Ca2+. The results indicate that the effects on lipid membrane surfaces by ions can directly affect myelin protein-membrane interactions at the molecular level, in addition to signalling effects in myelinating glia.