A Golgi-associated redox switch regulates ...
Document type :
Article dans une revue scientifique
Permalink :
Title :
A Golgi-associated redox switch regulates catalytic activation and cooperative functioning of ST6Gal-I with B4GalT-I
Author(s) :
Hassinen, Antti [Auteur]
Khoder-Agha, Fawzi [Auteur]
Khosrowabadi, Elham [Auteur]
Mennerich, Daniela [Auteur]
Harrus, Deborah [Auteur]
Noel, Maxence [Auteur]
Dimova, Elitsa Y. [Auteur]
Glumoff, Tuomo [Auteur]
Harduin Lepers, Anne [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Kietzmann, Thomas [Auteur]
Kellokumpu, Sakari [Auteur]
Khoder-Agha, Fawzi [Auteur]
Khosrowabadi, Elham [Auteur]
Mennerich, Daniela [Auteur]
Harrus, Deborah [Auteur]
Noel, Maxence [Auteur]
Dimova, Elitsa Y. [Auteur]
Glumoff, Tuomo [Auteur]
Harduin Lepers, Anne [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Kietzmann, Thomas [Auteur]
Kellokumpu, Sakari [Auteur]
Journal title :
Redox Biology
Abbreviated title :
Redox Biology
Volume number :
24
Pages :
101182
Publisher :
Elsevier BV
Publication date :
2019-06
ISSN :
2213-2317
English keyword(s) :
Hypoxia
Glycosylation
Golgi homeostasis
Redox state
Sialyltransferase
Glycosylation
Golgi homeostasis
Redox state
Sialyltransferase
HAL domain(s) :
Sciences du Vivant [q-bio]
Chimie/Chimie théorique et/ou physique
Chimie/Chimie théorique et/ou physique
English abstract : [en]
Glycosylation, a common modification of cellular proteins and lipids, is often altered in diseases and pathophysiological states such as hypoxia, yet the underlying molecular causes remain poorly understood. By utilizing ...
Show more >Glycosylation, a common modification of cellular proteins and lipids, is often altered in diseases and pathophysiological states such as hypoxia, yet the underlying molecular causes remain poorly understood. By utilizing lectin microarray glycan profiling, Golgi pH and redox screens, we show here that hypoxia inhibits terminal sialylation of N- and O-linked glycans in a HIF- independent manner by lowering Golgi oxidative potential. This redox state change was accompanied by loss of two surface-exposed disulfide bonds in the catalytic domain of the α-2,6-sialyltransferase (ST6Gal-I) and its ability to functionally interact with B4GalT-I, an enzyme adding the preceding galactose to complex N-glycans. Mutagenesis of selected cysteine residues in ST6Gal-I mimicked these effects, and also rendered the enzyme inactive. Cells expressing the inactive mutant, but not those expressing the wild type ST6Gal-I, were able to proliferate and migrate normally, supporting the view that inactivation of the ST6Gal-I help cells to adapt to hypoxic environment. Structure comparisons revealed similar disulfide bonds also in ST3Gal-I, suggesting that this O-glycan and glycolipid modifying sialyltransferase is also sensitive to hypoxia and thereby contribute to attenuated sialylation of O-linked glycans in hypoxic cells. Collectively, these findings unveil a previously unknown redox switch in the Golgi apparatus that is responsible for the catalytic activation and cooperative functioning of ST6Gal-I with B4GalT-I.Show less >
Show more >Glycosylation, a common modification of cellular proteins and lipids, is often altered in diseases and pathophysiological states such as hypoxia, yet the underlying molecular causes remain poorly understood. By utilizing lectin microarray glycan profiling, Golgi pH and redox screens, we show here that hypoxia inhibits terminal sialylation of N- and O-linked glycans in a HIF- independent manner by lowering Golgi oxidative potential. This redox state change was accompanied by loss of two surface-exposed disulfide bonds in the catalytic domain of the α-2,6-sialyltransferase (ST6Gal-I) and its ability to functionally interact with B4GalT-I, an enzyme adding the preceding galactose to complex N-glycans. Mutagenesis of selected cysteine residues in ST6Gal-I mimicked these effects, and also rendered the enzyme inactive. Cells expressing the inactive mutant, but not those expressing the wild type ST6Gal-I, were able to proliferate and migrate normally, supporting the view that inactivation of the ST6Gal-I help cells to adapt to hypoxic environment. Structure comparisons revealed similar disulfide bonds also in ST3Gal-I, suggesting that this O-glycan and glycolipid modifying sialyltransferase is also sensitive to hypoxia and thereby contribute to attenuated sialylation of O-linked glycans in hypoxic cells. Collectively, these findings unveil a previously unknown redox switch in the Golgi apparatus that is responsible for the catalytic activation and cooperative functioning of ST6Gal-I with B4GalT-I.Show less >
Language :
Anglais
Peer reviewed article :
Oui
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
Université de Lille
CNRS
CNRS
Research team(s) :
Régulation de la glycosylation terminale
Submission date :
2020-12-07T10:47:49Z
2020-12-07T18:07:59Z
2020-12-07T18:07:59Z
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