Univ. Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, Lille F-59000, France.
Univ. Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, Lille F-59000, France.
Biochim Biophys Acta Gen Subj. 2020 Oct;1864(10):129674. doi: 10.1016/j.bbagen.2020.129674. Epub 2020 Jun 26.
About half of the eukaryotic proteins bind biometals that participate in their structure and functions in virtually all physiological processes, including glycosylation. After reviewing the biological roles and transport mechanisms of calcium, magnesium, manganese, zinc and cobalt acting as cofactors of the metalloproteins involved in sugar metabolism and/or glycosylation, the paper will outline the pathologies resulting from a dysregulation of these metals homeostasis and more particularly Congenital Disorders of Glycosylation (CDGs) caused by ion transporter defects. Highlighting of CDGs due to defects in SLC39A8 (ZIP8) and TMEM165, two proteins transporting manganese from the extracellular space to cytosol and from cytosol to the Golgi lumen, respectively, has emphasized the importance of manganese homeostasis for glycosylation. Based on our current knowledge of TMEM165 structure and functions, this review will draw a picture of known and putative mechanisms regulating manganese homeostasis in the secretory pathway.
大约一半的真核生物蛋白与生物金属结合，这些金属参与了它们在几乎所有生理过程中的结构和功能，包括糖基化。在回顾了钙、镁、锰、锌和钴作为参与糖代谢和/或糖基化的金属蛋白的辅助因子的生物学作用和运输机制后，本文将概述这些金属稳态失调导致的病理学，特别是由于离子转运体缺陷引起的先天性糖基化障碍（CDGs）。由于 SLC39A8（ZIP8）和 TMEM165 缺陷引起的 CDGs 的突出表现，这两种蛋白分别将锰从细胞外空间运输到细胞质和从细胞质运输到高尔基体腔，强调了锰稳态对糖基化的重要性。基于我们目前对 TMEM165 结构和功能的了解，本综述将描绘出已知和假定的调节分泌途径中锰稳态的机制。
