Oligodendrocyte-lineage cell exocytosis and L-type prostaglandin D synthase promote oligodendrocyte development and myelination.
Oligodendrocyte-lineage cell exocytosis and L-type prostaglandin D synthase promote oligodendrocyte development and myelination.
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DOI：
10.7554/elife.77441
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发表时间：
2023-02-13
期刊：
影响因子：
7.7
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Pan L;Trimarco A;Zhang AJ;Fujimori K;Urade Y;Sun LO;Taveggia C;Zhang Y
在发育中的中枢神经系统中，少突胶质细胞前体细胞 (OPC) 分化为少突胶质细胞，在轴突周围形成髓磷脂。少突胶质细胞和髓鞘质对于中枢神经系统的功能至关重要，多发性硬化症和脑白质营养不良等脱髓鞘疾病中出现的严重神经系统症状就证明了这一点。尽管已经报道了许多调节少突胶质细胞发育和髓鞘形成的细胞内在机制，但少突胶质细胞谱系细胞（OPC和少突胶质细胞）之间的相互作用是否影响少突胶质细胞发育和髓鞘形成仍不清楚。在这里，我们发现，阻断少突胶质细胞系细胞的囊泡相关膜蛋白 (VAMP) 1/2/3 依赖性胞吐作用会损害小鼠少突胶质细胞的发育、髓鞘形成和运动行为。将少突胶质细胞谱系细胞分泌的分子添加到分泌缺陷的 OPC 培养物中可以部分恢复少突胶质细胞的形态成熟。此外，我们还发现 L 型前列腺素 D 合酶是一种少突胶质细胞谱系细胞分泌蛋白，可促进体内少突胶质细胞发育和髓鞘形成。这些发现揭示了一种新的自分泌/旁分泌环路模型，用于调节少突胶质细胞和髓鞘质的发育。
In the developing central nervous system, oligodendrocyte precursor cells (OPCs) differentiate into oligodendrocytes, which form myelin around axons. Oligodendrocytes and myelin are essential for the function of the central nervous system, as evidenced by the severe neurological symptoms that arise in demyelinating diseases such as multiple sclerosis and leukodystrophy. Although many cell-intrinsic mechanisms that regulate oligodendrocyte development and myelination have been reported, it remains unclear whether interactions among oligodendrocyte-lineage cells (OPCs and oligodendrocytes) affect oligodendrocyte development and myelination. Here, we show that blocking vesicle-associated membrane protein (VAMP) 1/2/3-dependent exocytosis from oligodendrocyte-lineage cells impairs oligodendrocyte development, myelination, and motor behavior in mice. Adding oligodendrocyte-lineage cell-secreted molecules to secretion-deficient OPC cultures partially restores the morphological maturation of oligodendrocytes. Moreover, we identified L-type prostaglandin D synthase as an oligodendrocyte-lineage cell-secreted protein that promotes oligodendrocyte development and myelination in vivo. These findings reveal a novel autocrine/paracrine loop model for the regulation of oligodendrocyte and myelin development.