Early stages of retinal development depend on Sec13 function.

Early stages of retinal development depend on Sec13 function.
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DOI:
10.1242/bio.20133251
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发表时间:
2013-03-15
期刊:
影响因子:
2.4
通讯作者:
Stephens DJ
Stephens DJ
中科院分区:
生物学4区
文献类型:
--
作者:
Schmidt K;Cavodeassi F;Feng Y;Stephens DJ

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ER到高尔基体的转运蛋白的目的地为细胞外空间或细胞内隔室依赖于COPII囊泡外套,是组成性的所有的细胞功能活跃的细胞。然而,有新的证据表明,这一过程是在细胞和组织特异性的基础上进行调节的,这意味着COPII涂层的组分对某些细胞类型具有不同的重要性。COPII涂层由内层Sec 23/24和外层Sec 13/31组成。我们之前已经表明,Sec 13的敲低导致Sec 31的伴随损失。在斑马鱼和培养的人类细胞中,这导致大货物(即前胶原)的运输受损,并且是颅面和肠道发育缺陷的原因。现在广泛接受的是,外部COPII外壳是包含大的、不寻常的货物蛋白的ER输出囊泡的结构和稳定性的关键。在这里,我们调查斑马鱼眼睛的发展Sec 13耗尽。我们发现光感受器从一开始就退化或无法发育。视网膜色素上皮细胞胶原运输受损和整体视网膜分层缺陷也见于Sec 13缺失的斑马鱼中,可能是由视网膜中细胞凋亡增加和局部增殖减少引起的。我们的数据表明,COPII外壳的外层也是运输大量货物蛋白质所必需的,在这种情况下是视紫红质,而不仅仅是以前认为的大型货物。
ER-to-Golgi transport of proteins destined for the extracellular space or intracellular compartments depends on the COPII vesicle coat and is constitutive in all translationally active cells. Nevertheless, there is emerging evidence that this process is regulated on a cell- and tissue-specific basis, which means that components of the COPII coat will be of differential importance to certain cell types. The COPII coat consists of an inner layer, Sec23/24 and an outer shell, Sec13/31. We have shown previously that knock-down of Sec13 results in concomitant loss of Sec31. In zebrafish and cultured human cells this leads to impaired trafficking of large cargo, namely procollagens, and is causative for defects in craniofacial and gut development. It is now widely accepted that the outer COPII coat is key to the architecture and stability of ER export vesicles containing large, unusual cargo proteins. Here, we investigate zebrafish eye development following Sec13 depletion. We find that photoreceptors degenerate or fail to develop from the onset. Impaired collagen trafficking from the retinal pigment epithelium and defects in overall retinal lamination also seen in Sec13-depleted zebrafish might have been caused by increased apoptosis and reduced topical proliferation in the retina. Our data show that the outer layer of the COPII coat is also necessary for the transport of large amounts of cargo proteins, in this case rhodopsin, rather than just large cargo as previously thought.
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