Uyemura K, Asou H, Takeda Y
Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
Prog Brain Res. 1995;105:311-8. doi: 10.1016/s0079-6123(08)63309-9.
(1) Two glycoproteins, P0 and PASII, are widely distributed in the peripheral myelin, but not in the central myelin of mammals. P0-like protein is expressed in both peripheral and central myelins of some lower vertebrates, such as fish and tadpoles. A close relationship is suggested between P0 expression and neural regenerative activity. (2) PMP22 was reported to show high sequence homology, not only to PASII, but also to the growth arrest specific protein. Human PASII/PMP22 sequence was deduced and the locus of its gene, chromosome 17p12-p11.2, is similar to the region linked to Charcot-Marie-Tooth disease type 1A. (3) P0 expressed on cultured cells mediated strong homophilic cell adhesion and neurite outgrowth. Addition of the P0 glycopeptide inhibited cell adhesion markedly, indicating that the oligosaccharide with peptide is essential for P0 mediated cell adhesion. The active site for neurite outgrowth in P0 appears to be different from the adhesion site. (4) We determined the human chromosomal locus of the P0 gene, 1q22-q23, which corresponded to the locus of hereditary motor and sensory neuropathy, Charcot-Marie-Tooth disease type 1B. Point mutations in the extracellular domain of P0 are found in the patient's chromosome. (5) L1 is a large multifunctional adhesive glycoprotein of 200 kD. Rat and human L1 sequences confirmed a common structure for the mammalian nervous systems. An isoform of L1 (L1cs), lacking four amino acids, appears to localize in non-neuronal cells such as Schwann cells, while the complete L1 is exclusively found in neurons. L1cs in Schwann cells may be functionally different from L1 in neurons.
(1) 两种糖蛋白，P0和PASII，广泛分布于哺乳动物的外周髓鞘，但不在中枢髓鞘中。类似P0的蛋白在一些低等脊椎动物（如鱼类和蝌蚪）的外周和中枢髓鞘中均有表达。提示P0表达与神经再生活性之间存在密切关系。(2) 据报道，PMP22不仅与PASII有高度序列同源性，还与生长停滞特异性蛋白有高度序列同源性。推导了人PASII/PMP22序列，其基因座位于染色体17p12 - p11.2，与1A型夏科 - 马里 - 图斯病相关区域相似。(3) 在培养细胞上表达的P0介导强烈的同种型细胞黏附和神经突生长。添加P0糖肽可显著抑制细胞黏附，表明糖肽寡糖对P0介导的细胞黏附至关重要。P0中神经突生长的活性位点似乎与黏附位点不同。(4) 我们确定了P0基因的人染色体基因座为1q22 - q23，这与遗传性运动和感觉神经病1B型（夏科 - 马里 - 图斯病）的基因座相对应。在患者染色体中发现了P0细胞外结构域的点突变。(5) L1是一种200 kD的大型多功能黏附糖蛋白。大鼠和人L1序列证实了哺乳动物神经系统的共同结构。一种缺少四个氨基酸的L1同工型（L1cs）似乎定位于非神经元细胞，如施万细胞，而完整的L1仅在神经元中发现。施万细胞中的L1cs在功能上可能与神经元中的L1不同。
