Departments of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
Department of Cell Biology, Yale University School of Medicine, New Haven, CT, USA.
Prog Mol Subcell Biol. 2021;59:163-180. doi: 10.1007/978-3-030-67696-4_8.
The endoplasmic reticulum (ER) performs key cellular functions including protein synthesis, lipid metabolism and signaling. While these functions are spatially isolated in structurally distinct regions of the ER, there is cross-talk between the pathways. One vital player that is involved in ER function is the ER-resident protein calreticulin (CALR). It is a calcium ion-dependent lectin chaperone that primarily assists in glycoprotein synthesis in the ER as part of the protein quality control machinery. CALR also buffers calcium ion release and mediates other glycan-independent protein interactions. Mutations in CALR have been reported in a subset of chronic blood tumors called myeloproliferative neoplasms. The mutations consist of insertions or deletions in the CALR gene that all cause a + 1 bp shift in the reading frame and lead to a dramatic alteration of the amino acid sequence of the C-terminal domain of CALR. This alters CALR function and affects cell homeostasis. This chapter will discuss how CALR and mutant CALR affect ER health and disease.
内质网 (ER) 执行关键的细胞功能，包括蛋白质合成、脂质代谢和信号转导。虽然这些功能在 ER 的结构上不同的区域中是空间隔离的，但途径之间存在着交叉对话。一种参与 ER 功能的重要蛋白是内质网驻留蛋白钙网织蛋白 (CALR)。它是一种钙离子依赖性凝集素伴侣，主要作为蛋白质质量控制机制的一部分，协助 ER 中糖蛋白的合成。CALR 还缓冲钙离子释放并介导其他糖非依赖性蛋白相互作用。CALR 突变已在一组称为骨髓增生性肿瘤的慢性血液肿瘤中报道。这些突变包括在 CALR 基因中的插入或缺失，这些突变都导致阅读框中的 +1 bp 移位，并导致 CALR C 末端结构域的氨基酸序列发生显著改变。这改变了 CALR 的功能并影响细胞内稳态。本章将讨论 CALR 和突变型 CALR 如何影响 ER 的健康和疾病。
