Myelin protein zero (P0), a type I transmembrane protein, is the most abundant protein in peripheral nervous system (PNS) myelin—the lipid-rich, periodic structure of membrane pairs that concentrically encloses long axonal segments. Schwann cells, the myelinating glia of the PNS, express P0 throughout their development until the formation of mature myelin. In the intramyelinic compartment, the immunoglobulin-like domain of P0 bridges apposing membranes via homophilic adhesion, forming, as revealed by electron microscopy, the electron-dense, double “intraperiod line” that is split by a narrow, electron-lucent space corresponding to the extracellular space between membrane pairs. The C-terminal tail of P0 adheres apposing membranes together in the narrow cytoplasmic compartment of compact myelin, much like myelin basic protein (MBP). In mouse models, the absence of P0, unlike that of MBP or P2, severely disturbs myelination. Therefore, P0 is the executive molecule of PNS myelin maturation. How and when P0 is trafficked and modified to enable myelin compaction, and how mutations that give rise to incurable peripheral neuropathies alter the function of P0, are currently open questions. The potential mechanisms of P0 function in myelination are discussed, providing a foundation for the understanding of mature myelin development and how it derails in peripheral neuropathies.

中文翻译：

---

零蛋白如何组装致密髓磷脂？


髓磷脂零蛋白 (P0) 是一种 I 型跨膜蛋白，是周围神经系统 (PNS) 髓磷脂中最丰富的蛋白质，髓磷脂是同心包围长轴突段的膜对的富含脂质的周期性结构。雪旺细胞（PNS 的髓鞘神经胶质细胞）在其整个发育过程中表达 P0，直至形成成熟的髓磷脂。在髓鞘内区室中，P0 的免疫球蛋白样结构域通过亲同性粘附桥接膜，形成电子致密的双“周期内线”，如电子显微镜所示，该线被狭窄的、电子透明的空间分开，该空间对应于膜对之间的细胞外空间。 P0 的 C 末端尾部在致密髓磷脂的狭窄细胞质室中将相邻的膜粘附在一起，就像髓磷脂碱性蛋白 (MBP) 一样。在小鼠模型中，与 MBP 或 P2 不同，P0 的缺失会严重干扰髓鞘形成。因此，P0是PNS髓磷脂成熟的执行分子。 P0 如何以及何时被运输和修饰以实现髓磷脂压缩，以及导致无法治愈的周围神经病变的突变如何改变 P0 的功能，这些都是目前悬而未决的问题。讨论了 P0 功能在髓鞘形成中的潜在机制，为理解成熟髓鞘发育及其在周围神经病中的脱轨奠定了基础。