Sec24 proteins and sorting at the endoplasmic reticulum

Sec24 proteins and sorting at the endoplasmic reticulum
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DOI:
10.1074/jbc.274.12.7833
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发表时间:
1999-03-19
影响因子:
4.8
通讯作者:
Paccaud, JP
Paccaud, JP
中科院分区:
生物学2区
文献类型:
--
作者:
Pagano, A;Letourneur, F;Paccaud, JP

文献摘要

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COPII 蛋白是在内质网产生分泌囊泡所必需的。在酵母中,Sec24p 蛋白是唯一已鉴定出两个密切直系同源物的 COPII 成分。通过在酵母中使用基因敲除,我们发现这些 Sec24 直向同源物之一的缺失导致释放到培养基中的一部分蛋白质的选择性分泌缺陷。数据库搜索揭示了人类、蠕虫、苍蝇和植物中存在整个 Sec24 相关蛋白家族。除了数据库中已经存在的两个人类 cDNA 之外,我们还鉴定并克隆了两个新的人类 cDNA,它们编码与酵母 Sec24p 同源的蛋白质。迄今为止鉴定的整个 Sec24 家族的特征是所有蛋白质的 2/3 羧基末端结构域内都有高度保守的残基簇和一个不同的氨基末端结构域。人 (h) Sec24 直系同源物与 hSec23Ap 共免疫沉淀,并通过尺寸排阻色谱法作为复合物迁移。免疫荧光显微镜证实这些蛋白质与 hSec23p 和 hSec13p 共定位。总之,我们的数据表明,除了在囊泡形成中的作用之外,Sec23-24p 复合物可能还与货物的选择和浓度有关。
COPII proteins are necessary to generate secretory vesicles at the endoplasmic reticulum, In yeast, the Sec24p protein is the only COPII component in which two close orthologues have been identified. By using gene knock-out in yeast, we found that the absence of one of these Sec24 orthologues resulted in a selective secretion defect for a subset of proteins released into the medium. Data base searches revealed the existence of an entire family of Sec24-related proteins in humans, worms, flies, and plants. We identified and cloned two new human cDNAs encoding proteins homologous to yeast Sec24p, in addition to two human cDNAs already present within the data bases. The entire Sec24 family identified to date is characterized by clusters of highly conserved residues within the 2/3 carboxyl-terminal domain of all the proteins and a divergent amino terminus domain. Human (h) Sec24 orthologues co-immunoprecipitate with hSec23Ap and migrate as a complex by size exclusion chromatography. Immunofluorescence microscopy confirmed that these proteins co-localize with hSec23p and hSec13p. Together, our data suggest that in addition to its role in the shaping up of the vesicle, the Sec23-24p complex may be implicated in cargo selection and concentration.