Efficient coupling of Sec23-Sec24 to Sec13-Sec31 drives COPII-dependent collagen secretion and is essential for normal craniofacial development
Efficient coupling of Sec23-Sec24 to Sec13-Sec31 drives COPII-dependent collagen secretion and is essential for normal craniofacial development
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DOI：
10.1242/jcs.031070
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发表时间：
2008-09-15
影响因子：
4
通讯作者：
Stephens, David J.
中科院分区：
文献类型：
--
作者：
Townley, Anna K.;Feng, Yi;Stephens, David J.
COPII外壳在内质网膜上组装，以协调分泌物的收集和运输囊泡的形成。在COPII组装过程中，Sar 1使膜变形并募集Sec 23-Sec 24复合物（Sec 23/24）和Sec 13-Sec 31（Sec 13/31），Sec 23-Sec 24复合物是系统的主要货物结合衔接子，Sec 13-Sec 31为囊泡形成提供结构外层。在这里，我们表明，Sec 13耗尽的结果在伴随的损失Sec 31和含Sec 23/24和货物的预出芽复合物的双核集群。电子显微镜显示存在的弯曲包被的配置文件上扩张的内质网，表明Sec 13/31是不需要的生成或维持的曲率。令人惊讶的是，出口tsO 45-G-YFP，分泌货物的标志物，是不受Sec 13/31耗尽;相比之下，从原代成纤维细胞的胶原蛋白的分泌强烈抑制。在斑马鱼中抑制Sec 13表达会导致蛋白多糖沉积缺陷和骨骼异常，这些异常与crusher突变斑马鱼和颅-颅-缝发育不良患者的颅面异常非常相似。我们的结论是，高效耦合的内部（Sec 23/24）和外部（Sec 13/31）层的COPII外套是必需的，以驱动出口的胶原蛋白从内质网，和高效COPII大会是必不可少的正常颅面发育在胚胎发生。
The COPII coat assembles on endoplasmic reticulum membranes to coordinate the collection of secretory cargo with the formation of transport vesicles. During COPII assembly, Sar1 deforms the membrane and recruits the Sec23-Sec24 complex (Sec23/24), which is the primary cargo-binding adaptor for the system, and Sec13-Sec31 (Sec13/31), which provides a structural outer layer for vesicle formation. Here we show that Sec13 depletion results in concomitant loss of Sec31 and juxtanuclear clustering of pre-budding complexes containing Sec23/24 and cargo. Electron microscopy reveals the presence of curved coated profiles on distended endoplasmic reticulum, indicating that Sec13/31 is not required for the generation or maintenance of the curvature. Surprisingly, export of tsO45-G-YFP, a marker of secretory cargo, is unaffected by Sec13/31 depletion; by contrast, secretion of collagen from primary fibroblasts is strongly inhibited. Suppression of Sec13 expression in zebrafish causes defects in proteoglycan deposition and skeletal abnormalities that are grossly similar to the craniofacial abnormalities of crusher mutant zebrafish and patients with cranio-lenticulo-sutural dysplasia. We conclude that efficient coupling of the inner (Sec23/24) and outer (Sec13/31) layers of the COPII coat is required to drive the export of collagen from the endoplasmic reticulum, and that highly efficient COPII assembly is essential for normal craniofacial development during embryogenesis.