Schwann cell myelination requires timely and precise targeting of P(0) protein.
Schwann cell myelination requires timely and precise targeting of P(0) protein.
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DOI：
10.1083/jcb.148.5.1009
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发表时间：
2000-03-06
影响因子：
7.8
通讯作者：
Trapp, B D
中科院分区：
文献类型：
--
作者：
Yin, X;Kidd, G J;Wrabetz, L;Feltri, M L;Messing, A;Trapp, B D
本文研究了过度表达P0（P0 tg）（PNS髓鞘的主要结构蛋白）的小鼠中雪旺细胞髓鞘形成失败的机制。定量超微结构免疫细胞化学证实，P0蛋白被错误地定位于髓鞘形成受阻的P0 tg雪旺细胞的轴突下膜、轴突周膜和轴突中膜。含P0的中间轴突膜的细胞外小叶与致密髓鞘的周期性紧密并列。髓鞘相关糖蛋白在高尔基体中被适当地分选，并靶向于轴周膜。在成年小鼠中，偶尔许旺氏细胞髓鞘轴突可能与援助的内吞去除的错误启动的P0。这些结果表明，P0基因增殖导致P0 mistargeting中轴突膜，并通过专性P0嗜同性粘附，使这些动态膜惰性和停止髓鞘形成。
This report investigated mechanisms responsible for failed Schwann cell myelination in mice that overexpress P0 (P0 tg), the major structural protein of PNS myelin. Quantitative ultrastructural immunocytochemistry established that P0 protein was mistargeted to abaxonal, periaxonal, and mesaxon membranes in P0 tg Schwann cells with arrested myelination. The extracellular leaflets of P0-containing mesaxon membranes were closely apposed with periodicities of compact myelin. The myelin-associated glycoprotein was appropriately sorted in the Golgi apparatus and targeted to periaxonal membranes. In adult mice, occasional Schwann cells myelinated axons possibly with the aid of endocytic removal of mistargeted P0. These results indicate that P0 gene multiplication causes P0 mistargeting to mesaxon membranes, and through obligate P0 homophilic adhesion, renders these dynamic membranes inert and halts myelination.