Novel alternatively spliced endoplasmic reticulum retention signal in the cytoplasmic loop of Proteolipid Protein-1.
Novel alternatively spliced endoplasmic reticulum retention signal in the cytoplasmic loop of Proteolipid Protein-1.
复制标题
Proteolipid Protein-1 细胞质环中的新型选择性剪接内质网保留信号。
DOI：
10.1002/jnr.21153
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发表时间：
2007
影响因子：
4.2
通讯作者：
Gow,Alexander
中科院分区：
文献类型：
--
作者：
Southwood,Cherie;Olson,Kevin;Wu,Chia-Yen;Gow,Alexander
对蛋白质折叠和运输对功能获得性疾病病因学的重要性的认识不断提高，推动了广泛的努力，以了解正常分泌途径蛋白质生命周期的细胞和分子生物学基础以及异常蛋白质的有害影响。在这方面，内质网（ER）中的质量控制机制已成为细胞确保分泌和跨膜蛋白采用稳定的二级，三级和四级结构或保留在ER中并降解的主要机制。在这里，我们研究了ER滞留在转染的成纤维细胞中的细胞和分子方面，这些成纤维细胞在蛋白脂质蛋白-1（PLP 1）基因中表达错义突变，导致人类轻度或严重形式的神经退行性疾病。轻度突变导致蛋白质滞留在ER中，这部分依赖于胞质暴露的七肽KGRGSRG的存在。相反，与严重突变相关的保留独立于该肽发生。因此，这种新的七肽的功能对发病机制具有显著影响，并为PLP 1基因编码的两种剪接异构体PLP 1和DM-20的功能提供了新的见解。© 2006 Wiley利斯公司
Increased awareness about the importance of protein folding and trafficking to the etiology of gain‐of‐function diseases has driven extensive efforts to understand the cell and molecular biology underlying the life cycle of normal secretory pathway proteins and the detrimental effects of abnormal proteins. In this regard, the quality‐control machinery in the endoplasmic reticulum (ER) has emerged as a major mechanism by which cells ensure that secreted and transmembrane proteins either adopt stable secondary, tertiary, and quaternary structures or are retained in the ER and degraded. Here we examine cellular and molecular aspects of ER retention in transfected fibroblasts expressing missense mutations in theProteolipid Protein‐1(PLP1) gene that cause mild or severe forms of neurodegenerative disease in humans. Mild mutations cause protein retention in the ER that is partially dependent on the presence of a cytoplasmically exposed heptapeptide, KGRGSRG. In contrast, retention associated with severe mutations occurs independently of this peptide. Accordingly, the function of this novel heptapeptide has a significant impact on pathogenesis and provides new insight into the functions of the two splice isoforms encoded by thePLP1gene, PLP1 and DM‐20. © 2006 Wiley‐Liss, Inc.