Scientists shed light on mystery behind myelin membrane synthesis
A set of protein processes needed in the early-stage conversion of glucose into fatty acids plays a central role in the proper formation and layering of myelin membrane, new research shows. The findings are part of the EU-funded AXON SUPPORT and NEUROMICS projects, which received EUR 1.3 million and EUR 1 million in support, respectively. The results, presented in the journal Proceedings of the National Academy of Sciences (PNAS), show how the use of X-rays uncovered how mutations affect the structure of myelin, an area of research crucial for neurological disorders. The researchers from Boston College in the US collaborated with colleagues in Italy, Japan, the Netherlands and Switzerland to evaluate how the composition of myelin lipids impacts the myelin structure and stability. The proper functioning of the body's nervous system relies on the myelin sheaths that surround the neurons' axons. 'Myelination requires a massive increase in glial cell membrane synthesis. Here, we demonstrate that the acute phase of myelin lipid synthesis is regulated by sterol regulatory element-binding protein (SREBP) cleavage activation protein (SCAP), an activator of SREBPs,' the authors of the study write. Boston College's Professor Daniel Kirschner said: 'Myelin is a stack of membranes providing insulation to the axon, and with that insulation comes rapid nerve conduction. If myelin becomes defective, the membranous insulator becomes leaky and the nerve doesn't conduct as well. If myelin is totally missing along part of an axon, the nerve conduction is blocked.' The team used X-ray diffraction to get a look at the dynamic membrane assembly in complete nerve samples obtained from mice engineered to mimic myelinic diseases. According to Professor Kirschner, when comparing X-ray diffraction with other microscopy techniques, the team found that the former provides fast, clean and clear results on the intermodal myelin's structural integrity. 'We were able to tell that the packing of the membranes was abnormal, which could affect the electrophysical properties of myelin,' the Boston College biologist said. 'We also saw that the packing of the lipids in the myelin lipid bilayers was more disordered in samples from the transgenic mice used here.' The researcher went on to say that other types of microscopy introduce chemical modifications to the tissue being evaluated. The molecular structure can be altered by these agents and by the time used to prepare and analyse the samples, which can also mask the dynamic interactions of myelin. 'X-ray diffraction requires no chemical treatments and can be completed in about an hour,' he said. 'The advantages of X-ray diffraction are that we can examine and analyse whole pieces of tissue and give information about the effect of the mutation on the native structure of the myelin as well as on its stability.' The research team has been using genetically altered mice for around four years as part of research into the role of myelin degeneration in various diseases of the central and peripheral nervous systems. AXON SUPPORT ('Axonuclear communication in health and disease') was funded under the 'New and emerging science and technology' (NEST) Thematic area of the EU's Sixth Framework Programme (FP6). NEUROMICS ('Functional genomics of the brain') was supported by the FP6's Marie Curie Actions - Early Stage Training.