Biometals and glycosylation in humans: Congenital disorders of glycosylation shed lights into the crucial role of Golgi manganese homeostasis.

Abstract

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.

• Authors: François Foulquier, Dominique Legrand
• Journal: Biochimica et biophysica acta. General subjects (Biochim Biophys Acta Gen Subj) Vol. 1864 Issue 10 Pg. 129674 (10 2020) ISSN: 1872-8006 [Electronic] Netherlands
• PMID: 32599014 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Antiporters
• Cation Transport Proteins
• SLC39A8 protein, human
• TMEM165 protein, human
• Manganese

Topics

• Animals
• Antiporters (metabolism)
• Biological Transport
• Cation Transport Proteins (metabolism)
• Congenital Disorders of Glycosylation (metabolism, pathology)
• Glycosylation
• Golgi Apparatus (metabolism, pathology)
• Homeostasis
• Humans
• Manganese (metabolism)