On the synergy between myelin proteins P0, MBP, and P2 in peripheral nerve major dense line formation

Abstract

Myelin is a proteolipid membrane multilayer held together by a set of proteins. The proper formation and function of the myelin sheath relies on the coordinated action of several key myelin proteins. Research exploring how proteins from the peripheral myelin cytoplasmic apposition - myelin basic protein (MBP), the cytoplasmic tail of myelin protein zero (P0ct), and peripheral myelin protein 2 (P2) - interact with each other and with myelin-like membranes was conducted using various techniques, such as small-angle X-ray diffraction (SAXD), differential scanning calorimetry (DSC), surface plasmon resonance (SPR), as well as electron and live epifluorescence microscopy. DSC revealed changes in lipid interactions depending on the protein combination, with MBP and P0ct binding more tightly to lipid membranes than P2, resulting in altered membrane fluidity and stability. These results were supported by SPR, which indicated that the myelin proteins may compete for membrane surface binding. Analysis of the Bragg peaks induced by the myelin proteins in lipidic environments showed both lamellar and non-lamellar phases in protein-lipid complexes. The results indicate both synergy and competition between the three main proteins residing in the PNS myelin major dense line. Furthermore, the observed direct effects of myelin proteins on lipid membrane properties may be relevant to their function in myelinating cells.