Martínez P, Ljungdahl P O
Ludwig Institute for Cancer Research, Box 240, S-17177 Stockholm, Sweden.
J Cell Sci. 2000 Dec;113 Pt 23:4351-62. doi: 10.1242/jcs.113.23.4351.
In Saccharomyces cerevisiae cells lacking SHR3, amino acid permeases do not enter into COPII transport vesicles and specifically accumulate in the membrane of the endoplasmic reticulum. Shr3p functions as a packaging chaperone to prime transport vesicle formation in the proximity of amino acid permeases. A genetic screen was developed that enabled the Schizosaccharomyces pombe SHR3 functional homologue, designated psh3(+) (pombe SHR3), to be cloned. The psh3(+) gene encodes a protein of 215 amino acids, which shares a high degree of structural and functional similarity with Shr3p. The heterologous expression of psh3(+) complements many, but not all, shr3 null mutant phenotypes in S. cerevisiae in a temperature-dependent manner. Psh3p is localised to the endoplasmic reticulum of S. pombe cells, and strains lacking the psh3(+ )gene exhibit decreased rates of amino acid uptake due to reduced levels of functional permeases in the plasma membrane. No packaging chaperones, or proteins exhibiting homology with packaging chaperones, have so far been identified in other eukayotic organisms. The findings reported here are the first to establish that specific packaging chaperones exist in divergent organisms, and demonstrate a conserved function of packaging chaperones in facilitating the export of large polytopic membrane proteins from the endoplasmic reticulum.
在缺乏SHR3的酿酒酵母细胞中，氨基酸通透酶不会进入COPII转运囊泡，而是特异性地积聚在内质网膜中。Shr3p作为一种包装伴侣蛋白，在氨基酸通透酶附近启动转运囊泡的形成。我们开发了一种遗传筛选方法，使得粟酒裂殖酵母SHR3的功能同源物（命名为psh3(+)，即粟酒裂殖酵母SHR3）得以克隆。psh3(+)基因编码一种由215个氨基酸组成的蛋白质，它与Shr3p在结构和功能上具有高度相似性。psh3(+)的异源表达以温度依赖的方式互补了酿酒酵母中许多（但不是全部）sh3缺失突变体表型。Psh3p定位于粟酒裂殖酵母细胞的内质网，缺乏psh3(+)基因的菌株由于质膜中功能性通透酶水平降低而表现出氨基酸摄取速率下降。到目前为止，在其他真核生物中尚未鉴定出包装伴侣蛋白或与包装伴侣蛋白具有同源性的蛋白质。本文报道的研究结果首次证实了不同生物中存在特异性包装伴侣蛋白，并证明了包装伴侣蛋白在促进多跨膜蛋白从内质网输出方面具有保守功能。
