The early secretory pathway, provisionally comprising of vesicular traffic between the endoplasmic reticulum (ER) and the Golgi apparatus, occurs constitutively in mammalian cells. Critical for a constant supply of secretory and plasma membrane (PM) materials, the pathway is presumably essential for general cellular function and survival. Neurons exhibit a high intensity in membrane dynamics and protein/lipid trafficking, with differential and polarized trafficking towards the somatodendritic and axonal PM domains. Mutations in genes encoding early secretory pathway membrane trafficking machinery components are known to result in neurodevelopmental or neurological disorders with disease manifestation in early life. Here, such rare disorders associated with autosomal recessive mutations in coat proteins, membrane tethering complexes and membrane fusion machineries responsible for trafficking in the early secretory pathway are summarily discussed. These mutations affected genes encoding subunits of coat protein complex I and II, subunits of transport protein particle (TRAPP) complexes, members of the YIP1 domain family (YIPF) and a SNAP receptor (SNARE) family member. Why the ubiquitously present and constitutively acting early secretory pathway machinery components could specifically affect neurodevelopment is addressed, with the plausible underlying disease etiologies and neuropathological mechanisms resulting from these mutations explored.

中文翻译：

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早期分泌途径转运机制成分和神经发育障碍的缺陷

早期分泌途径，暂时包括内质网 (ER) 和高尔基体之间的水泡交通，在哺乳动物细胞中组成性地发生。对于分泌和质膜 (PM) 材料的持续供应至关重要，该途径可能对一般细胞功能和生存至关重要。神经元在膜动力学和蛋白质/脂质运输中表现出高强度，具有向体树突和轴突 PM 结构域的差异和极化运输。已知编码早期分泌途径膜运输机制成分的基因突变会导致神经发育或神经系统疾病，并在生命早期出现疾病表现。在这里，这种罕见的疾病与外壳蛋白的常染色体隐性突变有关，简要讨论了负责在早期分泌途径中运输的膜束缚复合物和膜融合机制。这些突变影响编码外壳蛋白复合物 I 和 II 亚基、转运蛋白颗粒 (TRAPP) 复合物亚基、YIP1 结构域家族 (YIPF) 成员和 SNAP 受体 (SNARE) 家族成员的基因。为什么普遍存在和组成性作用的早期分泌途径机制成分可以特异性影响神经发育，并探讨了由这些突变引起的似是而非的潜在疾病病因和神经病理学机制。转运蛋白颗粒 (TRAPP) 复合物的亚基、YIP1 结构域家族 (YIPF) 的成员和 SNAP 受体 (SNARE) 家族的成员。为什么普遍存在和组成性作用的早期分泌途径机制成分可以特异性影响神经发育，并探讨了由这些突变引起的似是而非的潜在疾病病因和神经病理学机制。转运蛋白颗粒 (TRAPP) 复合物的亚基、YIP1 结构域家族 (YIPF) 的成员和 SNAP 受体 (SNARE) 家族的成员。为什么普遍存在和组成性作用的早期分泌途径机制成分可以特异性影响神经发育，并探讨了由这些突变引起的似是而非的潜在疾病病因和神经病理学机制。