Coat protein complex II (COPII) factors mediate cargo export from the endoplasmic reticulum (ER), but bulky collagens and lipoproteins are too large for traditional COPII vesicles. Mammalian CTAGE5 and TANGO1 have been well characterized individually as specialized cargo receptors at the ER that function with COPII coats to facilitate trafficking of bulky cargoes. Here, we present a genetic interaction study in zebrafish of deletions in ctage5, tango1, or both to investigate their potential distinct and complementary functions. We found that Ctage5 and Tango1 have different roles related to organogenesis, collagen versus lipoprotein trafficking, stress-pathway activation, and survival. While disruption of both ctage5 and tango1 compounded phenotype severity, mutation of either factor alone revealed novel tissue specific defects in the building of heart, muscle, lens, and intestine, in addition to the previously described roles in the development of neural and cartilage tissues. Together, our results demonstrate that Ctage5 and Tango1 have overlapping functions, but also suggest divergent roles in tissue development and homeostasis.

外壳蛋白复合物 II (COPII) 因子介导内质网 (ER) 的货物输出，但对于传统的 COPII 囊泡而言，庞大的胶原蛋白和脂蛋白太大。哺乳动物 CTAGE5 和 TANGO1 已被很好地表征为 ER 的专门货物受体，与 COPII 涂层一起工作以促进大宗货物的运输。在这里，我们在斑马鱼中进行了ctage5、tango1或两者缺失的遗传相互作用研究，以研究它们潜在的独特和互补功能。我们发现 Ctage5 和 Tango1 在器官发生、胶原蛋白与脂蛋白运输、应激通路激活和存活方面具有不同的作用。同时中断ctage5和tango1复合表型严重性，除了先前描述的在神经和软骨组织发育中的作用之外，单独的任一因子的突变揭示了心脏、肌肉、晶状体和肠的构建中的新的组织特异性缺陷。总之，我们的结果表明 Ctage5 和 Tango1 具有重叠的功能，但也表明在组织发育和体内平衡中的不同作用。