Hammer J A, O'Shannessy D J, De Leon M, Gould R, Zand D, Daune G, Quarles R H
Laboratory of Molecular and Cellular Neurobiology, NINDS, NIH, Bethesda, Maryland 20892.
J Neurosci Res. 1993 Aug 1;35(5):546-58. doi: 10.1002/jnr.490350511.
Mammalian peripheral nervous system (PNS) myelin contains several glycoproteins with molecular weights of 19 to 28 kDa, including the major 28 kDa P0 glycoprotein and a recently cloned protein called PMP-22. Some glycoproteins in this M(r) range in humans, cats and some other mammals react with HNK1, a mouse monoclonal antibody that identifies a carbohydrate epitope shared between the immune system and a number of adhesion proteins in the nervous system. A variety of antibodies to P0, PMP-22, and the carbohydrate determinants reacting with HNK1 were used to characterize immunochemically these 19 to 28 kDa glycoproteins of cat PNS myelin. The HNK1-reactive components include P0 and two slightly smaller 23 to 26 kDa proteins that are immunologically related to P0. However, HNK1 reacts most strongly with a lower molecular weight glycoprotein that does not react with the antibodies to P0 and was identified as PMP-22. Since the carbohydrate structure reacting with HNK1 is generally expressed on adhesion molecules, this result suggests that PMP-22 may function in cell-cell or membrane-membrane interactions. Furthermore, the related human anti-MAG monoclonal IgM antibodies from patients with neuropathy also react strongly with PMP-22, suggesting that it may be a target antigen in the pathogenesis of this disease. Purified PNS and CNS myelin from bony fish (toadfish and trout) were also shown to contain major glycoproteins, in the same 19 to 28 kDa M(r) range, that react very strongly with HNK1. It is shown that fish myelin has major proteins of this size that are immunologically and structurally related to mammalian P0, and it is demonstrated here that one of the strongly HNK1-positive proteins reacted well with an antiserum raised to bovine P0. The presence of high levels of the adhesion-related HNK1 epitope on these major myelin proteins of fish suggests that this carbohydrate structure may have played a role in the molecular evolution of myelin.
哺乳动物外周神经系统（PNS）髓鞘含有几种分子量为19至28 kDa的糖蛋白，包括主要的28 kDa P0糖蛋白和一种最近克隆的名为PMP - 22的蛋白。在人类、猫和其他一些哺乳动物中，这个分子量范围内的一些糖蛋白与HNK1发生反应，HNK1是一种小鼠单克隆抗体，可识别免疫系统与神经系统中许多粘附蛋白之间共有的碳水化合物表位。使用多种针对P0、PMP - 22以及与HNK1反应的碳水化合物决定簇的抗体，对猫PNS髓鞘的这些19至28 kDa糖蛋白进行免疫化学表征。与HNK1反应的成分包括P0以及另外两种略小的23至26 kDa蛋白，它们在免疫上与P0相关。然而，HNK1与一种分子量较低的糖蛋白反应最强，该糖蛋白不与针对P0的抗体反应，被鉴定为PMP - 22。由于与HNK1反应的碳水化合物结构通常在粘附分子上表达，这一结果表明PMP - 22可能在细胞 - 细胞或膜 - 膜相互作用中发挥作用。此外，来自神经病患者的相关人类抗MAG单克隆IgM抗体也与PMP - 22强烈反应，表明它可能是该疾病发病机制中的靶抗原。还显示来自硬骨鱼（蟾鱼和鳟鱼）的纯化PNS和CNS髓鞘含有主要糖蛋白，分子量范围相同，为19至28 kDa，它们与HNK1反应非常强烈。研究表明，鱼类髓鞘具有这种大小的主要蛋白，它们在免疫和结构上与哺乳动物P0相关，并且在此证明其中一种HNK1强阳性蛋白与针对牛P0产生的抗血清反应良好。鱼类这些主要髓鞘蛋白上高水平的与粘附相关的HNK1表位的存在表明，这种碳水化合物结构可能在髓鞘的分子进化中发挥了作用。
