Department of Cell Biology, Harvard Medical School, Blavatnik Institute, Boston, Massachusetts 02115, USA.
Department of Cell Biology, Harvard Medical School, Blavatnik Institute, Boston, Massachusetts 02115, USA
Cold Spring Harb Perspect Biol. 2023 Mar 1;15(3):a041249. doi: 10.1101/cshperspect.a041249.
High-fidelity protein localization is essential to define the identities and functions of different organelles and to maintain cellular homeostasis. Accurate localization of nascent proteins requires specific protein targeting pathways as well as quality control (QC) mechanisms to remove mislocalized proteins. The endoplasmic reticulum (ER) is the first destination for approximately one-third of the eukaryotic proteome and a major site of protein biosynthesis and QC. In mammalian cells, trafficking from the ER provides nascent proteins access to the extracellular space and essentially every cellular membrane and organelle except for mitochondria and possibly peroxisomes. Here, we discuss the biosynthetic mechanisms that deliver nascent proteins to the ER and the QC mechanisms that interface with the ER to correct or degrade mislocalized proteins.
高保真的蛋白质定位对于确定不同细胞器的身份和功能以及维持细胞内稳态至关重要。新生蛋白质的准确定位需要特定的蛋白质靶向途径以及质量控制(QC)机制来去除定位错误的蛋白质。内质网(ER)是大约三分之一真核生物蛋白质组的第一个目的地,也是蛋白质生物合成和 QC 的主要场所。在哺乳动物细胞中,从 ER 的运输为新生蛋白质提供了进入细胞外空间以及除线粒体和可能的过氧化物酶体外的几乎所有细胞膜和细胞器的途径。在这里,我们讨论了将新生蛋白质递送至 ER 的生物合成机制以及与 ER 相互作用以纠正或降解定位错误蛋白质的 QC 机制。