Denninger Andrew R, Demé Bruno, Cristiglio Viviana, LeDuc Géraldine, Feller W Bruce, Kirschner Daniel A
Biology Department, Boston College, Chestnut Hill, MA 02467, USA.
Institut Laue-Langevin (ILL), CS 20156, F-38042 Grenoble CEDEX 9, France.
Acta Crystallogr D Biol Crystallogr. 2014 Dec 1;70(Pt 12):3198-211. doi: 10.1107/S1399004714023815. Epub 2014 Nov 22.
Rapid nerve conduction in the central and peripheral nervous systems (CNS and PNS, respectively) of higher vertebrates is brought about by the ensheathment of axons with myelin, a lipid-rich, multilamellar assembly of membranes. The ability of myelin to electrically insulate depends on the regular stacking of these plasma membranes and on the presence of a number of specialized membrane-protein assemblies in the sheath, including the radial component, Schmidt-Lanterman incisures and the axo-glial junctions of the paranodal loops. The disruption of this fine-structure is the basis for many demyelinating neuropathies in the CNS and PNS. Understanding the processes that govern myelin biogenesis, maintenance and destabilization requires knowledge of myelin structure; however, the tight packing of internodal myelin and the complexity of its junctional specializations make myelin a challenging target for comprehensive structural analysis. This paper describes an examination of myelin from the CNS and PNS using neutron diffraction. This investigation revealed the dimensions of the bilayers and aqueous spaces of myelin, asymmetry between the cytoplasmic and extracellular leaflets of the membrane, and the distribution of water and exchangeable hydrogen in internodal multilamellar myelin. It also uncovered differences between CNS and PNS myelin in their water-exchange kinetics.
高等脊椎动物中枢神经系统(CNS)和周围神经系统(PNS)中神经冲动的快速传导是由轴突被髓鞘包裹实现的,髓鞘是一种富含脂质的多层膜结构。髓鞘的电绝缘能力取决于这些质膜的规则堆叠以及鞘中一些特殊膜蛋白组装体的存在,包括放射状成分、施密特-兰特尔曼切迹和结旁环的轴突-神经胶质连接。这种精细结构的破坏是中枢神经系统和周围神经系统中许多脱髓鞘性神经病的基础。了解髓鞘生物发生、维持和不稳定的过程需要了解髓鞘结构;然而,节间髓鞘的紧密堆积及其连接特化的复杂性使得髓鞘成为全面结构分析的一个具有挑战性的目标。本文描述了使用中子衍射对中枢神经系统和周围神经系统髓鞘的研究。这项研究揭示了髓鞘双层膜和水空间的尺寸、膜细胞质小叶和细胞外小叶之间的不对称性,以及节间多层髓鞘中水和可交换氢的分布。它还揭示了中枢神经系统和周围神经系统髓鞘在水交换动力学方面的差异。