Functional relationship between calreticulin, calnexin, and the endoplasmic reticulum luminal domain of calnexin
Functional relationship between calreticulin, calnexin, and the endoplasmic reticulum luminal domain of calnexin
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DOI：
10.1074/jbc.275.17.13089
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发表时间：
2000-04-28
影响因子：
4.8
通讯作者：
Williams, DB
中科院分区：
文献类型：
--
作者：
Danilczyk, UG;Cohen-Doyle, MF;Williams, DB
钙连接蛋白是内质网（ER）的膜蛋白，其作为分子伴侣和作为ER质量控制机制的组分起作用。钙网蛋白是钙连接蛋白的一种可溶性类似物，被认为具有类似的功能，但这些功能尚未在体内直接证实。这两种蛋白质都含有一个凝集素位点，该位点指导它们与新合成的糖蛋白的结合。虽然许多糖蛋白结合钙连接蛋白和钙网蛋白，但每种结合的糖蛋白谱存在差异。使用果蝇表达系统和小鼠I类组织相容性分子作为模型糖蛋白，我们发现钙网蛋白确实具有明显的分子伴侣和质量控制功能，增强I类折叠和亚基组装，稳定亚基，并阻碍出口的组装中间体从ER。事实上，钙连接蛋白和钙网蛋白的功能在很大程度上是可以互换的。我们还确定了钙连接蛋白的可溶性形式（残基1-387）可以在功能上取代其膜结合的对应物。然而，当钙连接蛋白在L细胞中表达为可溶性蛋白时，相关糖蛋白的模式改变为类似于钙网蛋白的模式。相反，膜锚定钙网蛋白结合到一组类似的糖蛋白钙连接蛋白。因此，钙连接蛋白和钙网蛋白的不同拓扑环境在确定其不同的底物特异性方面是重要的。
Calnexin is a membrane protein of the endoplasmic reticulum (ER) that functions as a molecular chaperone and as a component of the ER quality control machinery. Calreticulin, a soluble analog of calnexin, is thought to possess similar functions, but these have not been directly demonstrated in vivo. Both proteins contain a lectin site that directs their association with newly synthesized glycoproteins. Although many glycoproteins bind to both calnexin and calreticulin, there are differences in the spectrum of glycoproteins that each binds. Using a Drosophila expression system and the mouse class I histocompatibility molecule as a model glycoprotein, we found that calreticulin does possess apparent chaperone and quality control functions, enhancing class I folding and subunit assembly, stabilizing subunits, and impeding export of assembly intermediates from the ER. Indeed, the functions of calnexin and calreticulin were largely interchangeable. We also determined that a soluble form of calnexin (residues 1-387) can functionally replace its membrane-bound counterpart. However, when calnexin was expressed as a soluble protein in L cells, the pattern of associated glycoproteins changed to resemble that of calreticulin. Conversely, membrane-anchored calreticulin bound to a similar set of glycoproteins as calnexin. Therefore, the different topological environments of calnexin and calreticulin are important in determining their distinct substrate specificities.