Differential requirements for COPI transport during vertebrate early development
Differential requirements for COPI transport during vertebrate early development
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DOI：
10.1016/j.devcel.2004.07.020
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发表时间：
2004-10-01
影响因子：
11.8
通讯作者：
Stemple, DL
中科院分区：
文献类型：
--
作者：
Coutinho, P;Parsons, MJ;Stemple, DL
真核细胞中的被膜囊泡状被膜复合体是正常高尔基体和分泌活动所必需的。通过定位克隆控制斑马鱼脊索发育的基因，我们发现sneezy、happy和dopey位点编码被膜复合体的α、β和β '亚基。从突变体内质网的输出被阻断，高尔基体结构被破坏，并且突变体胚胎最终由于广泛的凋亡而退化。然而，早期胚胎表型表明，尽管其“管家”功能，coatomer活性是具体的和细胞自主需要正常的脊索中胚层分化，perinotochordal基底膜的形成，和黑色素细胞色素沉着。因此，胚胎组织对被膜活性的不同要求导致组织特异性发育缺陷。此外，我们注意到，编码α coatomer的mRNA在脊索祖细胞中显著上调，我们目前的数据表明，coatomer转录调整到活动和细胞类型特异性分泌负荷。
The coatomer vesicular coat complex is essential for normal Golgi and secretory activities in eukaryotic cells. Through positional cloning of genes controlling zebrafish notochord development, we found that the sneezy, happy, and dopey loci encode the alpha, beta, and beta' subunits of the coatomer complex. Export from mutant endoplasmic reticulum is blocked, Golgi structure is disrupted, and mutant embryos eventually degenerate due to widespread apoptosis. The early embryonic phenotype, however, demonstrates that despite its "housekeeping" functions, coatomer activity is specifically and cell autonomously required for normal chordamesoderm differentiation, perinotochordal basement membrane formation, and melanophore pigmentation. Hence, differential requirements for coatomer activity among embryonic tissues lead to tissue-specific developmental defects. Moreover, we note that the mRNA encoding alpha coatomer is strikingly upregulated in notochord progenitors, and we present data suggesting that a coatomer transcription is tuned to activity- and cell type-specific secretory loads.