Takeda Y, Notsu T, Kitamura K, Uyemura K
Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
Neurochem Res. 2001 Jun;26(6):599-607. doi: 10.1023/a:1010927001378.
Two major glycoproteins, P0 and PASII/PMP22, are specifically expressed in peripheral myelin. Point mutations of these proteins and over or under expression of PASII/PMP22 cause various hereditary peripheral neuropathies. P0 is well characterized as a major adhesion molecule in PNS myelin, but the function of PASII/PMP22 is still unknown. Recently, an oligodendrocyte-specific protein (OSP) was identified as a member of the claudin family and as a component of tight junctions of central myelins. Since PASII/PMP22 shows similarity in structure to OSP, which is a tetraspan membrane protein, we speculated if PASII/PMP22 could be a member of claudin superfamily. The primary structure of PASII/PMP22 showed a significant homology of 48% and a 21% identity with the OSP sequence. Exogenous expression of PASII/PMP22 in C6 cells significantly inhibited BrdU incorporation to the cells. The C6 cells stably transfected with PASII/PMP22 cDNA showed no homophilic cell adhesive activity. When dorsal root ganglion (DRG) neurons were cocultured on PASII/PMP22 expressing cells, both neurite extension and branching of DRG neurons were significantly inhibited. These results indicate that PASII/PMP22 may play a role in a turning point of Schwann cell development from proliferation to differentiation. On the other hand, the cells expressing claudin family proteins are reported to show strong cell adhesive activity and an ability to form tight junctions with neighboring cells. For this reason, we currently do not have any functional data supporting that PASII/PMP22 is the member of claudin superfamily.
两种主要的糖蛋白，P0和PASII/PMP22，在外周髓鞘中特异性表达。这些蛋白的点突变以及PASII/PMP22的过表达或低表达会导致各种遗传性周围神经病。P0作为周围神经系统髓鞘中的主要黏附分子已得到充分表征，但PASII/PMP22的功能仍不清楚。最近，一种少突胶质细胞特异性蛋白（OSP）被鉴定为claudin家族的成员以及中枢髓鞘紧密连接的一个组成部分。由于PASII/PMP22在结构上与作为四跨膜蛋白的OSP相似，我们推测PASII/PMP22是否可能是claudin超家族的成员。PASII/PMP22的一级结构与OSP序列显示出48%的显著同源性和21%的一致性。PASII/PMP22在C6细胞中的外源性表达显著抑制了BrdU掺入细胞。稳定转染PASII/PMP22 cDNA的C6细胞未显示出嗜同性细胞黏附活性。当背根神经节（DRG）神经元与表达PASII/PMP22的细胞共培养时，DRG神经元的神经突延伸和分支均受到显著抑制。这些结果表明，PASII/PMP22可能在雪旺细胞从增殖到分化的发育转折点中发挥作用。另一方面，据报道，表达claudin家族蛋白的细胞显示出很强的细胞黏附活性以及与相邻细胞形成紧密连接的能力。因此，我们目前没有任何功能数据支持PASII/PMP22是claudin超家族的成员。
