Department of Microbiology and Immunology, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA.
Department of Pharmacology, Brehm Diabetes Research Center, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA.
Prog Mol Subcell Biol. 2021;59:145-162. doi: 10.1007/978-3-030-67696-4_7.
The endoplasmic reticulum (ER) is an organelle that mediates the proper folding and assembly of proteins destined for the cell surface, the extracellular space and subcellular compartments such as the lysosomes. The ER contains a wide range of molecular chaperones to handle the folding requirements of a diverse set of proteins that traffic through this compartment. The lectin-like chaperones calreticulin and calnexin are an important class of structurally-related chaperones relevant for the folding and assembly of many N-linked glycoproteins. Despite the conserved mechanism of action of these two chaperones in nascent protein recognition and folding, calreticulin has unique functions in cellular calcium signaling and in the immune response. The ER-related functions of calreticulin in the assembly of major histocompatibility complex (MHC) class I molecules are well-studied and provide many insights into the modes of substrate and co-chaperone recognition by calreticulin. Calreticulin is also detectable on the cell surface under some conditions, where it induces the phagocytosis of apoptotic cells. Furthermore, mutations of calreticulin induce cell transformation in myeloproliferative neoplasms (MPN). Studies of the functions of the mutant calreticulin in cell transformation and immunity have provided many insights into the normal biology of calreticulin, which are discussed.
内质网（ER）是一种细胞器，介导细胞表面、细胞外空间和溶酶体等亚细胞隔室中预定用于蛋白质的正确折叠和组装。ER 包含广泛的分子伴侣，以处理通过该隔室运输的各种蛋白质的折叠要求。类似凝集素的伴侣蛋白钙网蛋白和钙联蛋白是与许多 N 连接糖蛋白折叠和组装相关的一类重要的结构相关伴侣蛋白。尽管这两种伴侣蛋白在新生蛋白识别和折叠中的作用机制保守，但钙网蛋白在细胞钙信号转导和免疫反应中具有独特的功能。钙网蛋白在主要组织相容性复合物（MHC）I 类分子组装中的 ER 相关功能得到了很好的研究，为钙网蛋白对底物和共伴侣蛋白的识别模式提供了许多见解。钙网蛋白在某些条件下也可检测到在细胞表面，在这些条件下，它可诱导凋亡细胞的吞噬作用。此外，钙网蛋白的突变可诱导骨髓增生性肿瘤（MPN）中的细胞转化。对突变钙网蛋白在细胞转化和免疫中的功能的研究为钙网蛋白的正常生物学提供了许多见解，对此进行了讨论。
