Myelin Basic Protein and Myelin Protein 2 Act Synergistically to Cause Stacking of Lipid Bilayers

Abstract

Saltatory conduction of nerve impulses along axonal membranes depends on the presence of a multilayered membrane, myelin, that wraps around the axon. Myelin basic protein (MBP) and myelin protein 2 (P2) are intimately involved in the generation of the myelin sheath. They are also implicated in a number of neurological diseases, including autoimmune diseases of both the central and peripheral nervous systems. Here, we have used atomic force microsopy (AFM) to study the effects of MBP and P2 on lipid bilayers. MBP in association with a mica substrate appeared unstructured, and tended to coat the mica surface in the form of a monolayer. In contrast, P2 appeared as discrete particles, with molecular volumes consistent with the formation of both monomers and dimers. Either MBP or P2, at micromolar concentrations, caused stacking of brain lipid bilayers. This stacking effect was significantly potentiated when both proteins were added together. Bilayers composed of phosphatidylcholine (PC) and phosphatidylserine (PS) were stacked by MBP, provided that cholesterol was also present; in contrast, P2 did not stack PC/PS/cholesterol bilayers. Hence, the bilayer stacking effects of the two proteins have different lipid requirements.

A role of peripheral myelin protein 2 in lipid homeostasis of myelinating schwann cells

“…Recent biochemical data suggested that Mbp might interact with Pmp2 to form and maintain compact myelin (Suresh et al, 2010). Interestingly, shiverer mice (carriers of an autosomal recessive mutation for Mbp) possess severe myelin defects in the CNS, but not in the PNS (Dupouey et al, 1979;Mikoshiba et al, 1981).…”

“…6c and a detailed list of lipid species contributing more than 0.5% to the total mass spectrometry signal is provided in Supporting Information Table S1. Pmp2 is known to bind fatty acids (Maddalo et al, 2010;Sedzik and Jastrzebski, 2011;Uyemura et al, 1984) and to interact with membrane bilayers (Ruskamo et al, 2014;Suresh et al, 2010). We therefore further explored the role of Pmp2 in lipid transport to or from membrane vesicles by using the fluorescent fatty acid analog DAUDA.…”

Neutron scattering studies on protein dynamics using the human myelin peripheral membrane protein P2

“…P2 is known to stack lipid bilayers together [7,11] and stabilize the membrane structure [12]. Previous neutron scattering studies have shown that P2 bound to myelinmimicking vesicles made either of 1,2-dimyristoyl-snglycero-3-phosphatidic acid (DMPA) or of a binary mixture of 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), respectively, reduces the lipid dynamics [13].…”

The Influence of the Myelin Basic Protein C8 Mutant on the Dynamics of Myelin Membranes

“…MBP-C1 and MBP-C8 were prepared as described elsewhere [13]. For membrane samples, large multilamellar vesicles (ULVs) of DOPS:DOPC lipids were prepared by dissolving the lipids in chloroform (in a 1:1 mass ratio).…”