Yin Xinghua, Baek Rena C, Kirschner Daniel A, Peterson Alan, Fujii Yasuhisa, Nave Klaus-Armin, Macklin Wendy B, Trapp Bruce D
Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
J Cell Biol. 2006 Jan 30;172(3):469-78. doi: 10.1083/jcb.200509174.
The central nervous system (CNS) of terrestrial vertebrates underwent a prominent molecular change when a tetraspan membrane protein, myelin proteolipid protein (PLP), replaced the type I integral membrane protein, P0, as the major protein of myelin. To investigate possible reasons for this molecular switch, we genetically engineered mice to express P0 instead of PLP in CNS myelin. In the absence of PLP, the ancestral P0 provided a periodicity to mouse compact CNS myelin that was identical to mouse PNS myelin, where P0 is the major structural protein today. The PLP-P0 shift resulted in reduced myelin internode length, degeneration of myelinated axons, severe neurological disability, and a 50% reduction in lifespan. Mice with equal amounts of P0 and PLP in CNS myelin had a normal lifespan and no axonal degeneration. These data support the hypothesis that the P0-PLP shift during vertebrate evolution provided a vital neuroprotective function to myelin-forming CNS glia.
当一种四跨膜蛋白——髓磷脂蛋白脂蛋白（PLP）取代I型整合膜蛋白P0，成为髓磷脂的主要蛋白时，陆生脊椎动物的中枢神经系统（CNS）发生了显著的分子变化。为了探究这种分子转换的可能原因，我们通过基因工程改造小鼠，使其在中枢神经系统髓磷脂中表达P0而非PLP。在没有PLP的情况下，祖先型P0为小鼠紧密的中枢神经系统髓磷脂提供了一种周期性，这与小鼠周围神经系统（PNS）髓磷脂相同，而P0如今是PNS髓磷脂的主要结构蛋白。PLP向P0的转变导致髓鞘节间长度缩短、有髓轴突退化、严重的神经功能障碍以及寿命缩短50%。中枢神经系统髓磷脂中P0和PLP含量相等的小鼠寿命正常，且没有轴突退化。这些数据支持了这样一种假说，即在脊椎动物进化过程中，P0向PLP的转变为形成髓磷脂的中枢神经系统胶质细胞提供了至关重要的神经保护功能。
