Pagano A, Letourneur F, Garcia-Estefania D, Carpentier J L, Orci L, Paccaud J P
Department of Morphology, University Medical Center, Geneva University, Geneva CH-1211, Switzerland.
J Biol Chem. 1999 Mar 19;274(12):7833-40. doi: 10.1074/jbc.274.12.7833.
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.
COPII蛋白对于在内质网产生分泌囊泡是必需的。在酵母中，Sec24p蛋白是唯一已鉴定出两个紧密直系同源物的COPII组分。通过在酵母中使用基因敲除，我们发现缺失这些Sec24直系同源物之一会导致释放到培养基中的一部分蛋白质出现选择性分泌缺陷。数据库搜索揭示了在人类、蠕虫、果蝇和植物中存在一个完整的Sec24相关蛋白家族。除了数据库中已有的两个人类cDNA外，我们还鉴定并克隆了两个新的编码与酵母Sec24p同源蛋白的人类cDNA。迄今为止鉴定出的整个Sec24家族的特征是所有蛋白质的2/3羧基末端结构域内存在高度保守的残基簇和一个不同的氨基末端结构域。人类（h）Sec24直系同源物与hSec23Ap共免疫沉淀，并通过尺寸排阻色谱法以复合物形式迁移。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外，Sec23 - 24p复合物可能还参与货物选择和浓缩。
