Insights into the regulation of cellular ...
Document type :
Article dans une revue scientifique: Article original
Permalink :
Title :
Insights into the regulation of cellular Mn2+ homeostasis via TMEM165
Author(s) :
Vicogne, Dorothee [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Beauval, Nicolas [Auteur]
IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483
Durin, Zoe [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Allorge, Delphine [Auteur]
IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483
Kondratska, Kateryna [Auteur]
Haustrate, Aurélien [Auteur]
Prevarskaya, Natasha [Auteur]
Lupashin, Vladimir [Auteur]
Legrand, Dominique [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Foulquier, Francois [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Beauval, Nicolas [Auteur]

IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483
Durin, Zoe [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Allorge, Delphine [Auteur]

IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483
Kondratska, Kateryna [Auteur]
Haustrate, Aurélien [Auteur]
Prevarskaya, Natasha [Auteur]
Lupashin, Vladimir [Auteur]
Legrand, Dominique [Auteur]

Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Foulquier, Francois [Auteur]

Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Journal title :
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Abbreviated title :
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Volume number :
1869
Pages :
166717
Publisher :
Elsevier BV
Publication date :
2023-08
ISSN :
0925-4439
English keyword(s) :
TMEM165
CDG
Glycosylation
SPCA1
Manganese
Golgi
CDG
Glycosylation
SPCA1
Manganese
Golgi
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Golgi cation homeostasis is known to be crucial for many cellular processes including vesicular fusion events, protein secretion, as well as for the activity of Golgi glycosyltransferases and glycosidases. TMEM165 was ...
Show more >Golgi cation homeostasis is known to be crucial for many cellular processes including vesicular fusion events, protein secretion, as well as for the activity of Golgi glycosyltransferases and glycosidases. TMEM165 was identified in 2012 as the first cation transporter related to human glycosylation diseases, namely the Congenital Disorders of Glycosylation (CDG). Interestingly, divalent manganese (Mn) supplementation has been shown to suppress the observed glycosylation defects in TMEM165-deficient cell lines, thus suggesting that TMEM165 is involved in cellular Mn homeostasis. This paper demonstrates that the origin of the Golgi glycosylation defects arises from impaired Golgi Mn homeostasis in TMEM165-depleted cells. We show that Mn supplementation fully rescues the Mn content in the secretory pathway/organelles of TMEM165-depleted cells and hence the glycosylation process. Strong cytosolic and organellar Mn accumulations can also be observed in TMEM165- and SPCA1-depleted cells upon incubation with increasing Mn concentrations, thus demonstrating the crucial involvement of these two proteins in cellular Mn homeostasis. Interestingly, our results show that the cellular Mn homeostasis maintenance in control cells is correlated with the presence of TMEM165 and that the Mn-detoxifying capacities of cells, through the activity of SPCA1, rely on the Mn-induced degradation mechanism of TMEM165. Finally, this paper highlights that TMEM165 is essential in secretory pathway/organelles Mn homeostasis maintenance to ensure both Golgi glycosylation enzyme activities and cytosolic Mn detoxification.Show less >
Show more >Golgi cation homeostasis is known to be crucial for many cellular processes including vesicular fusion events, protein secretion, as well as for the activity of Golgi glycosyltransferases and glycosidases. TMEM165 was identified in 2012 as the first cation transporter related to human glycosylation diseases, namely the Congenital Disorders of Glycosylation (CDG). Interestingly, divalent manganese (Mn) supplementation has been shown to suppress the observed glycosylation defects in TMEM165-deficient cell lines, thus suggesting that TMEM165 is involved in cellular Mn homeostasis. This paper demonstrates that the origin of the Golgi glycosylation defects arises from impaired Golgi Mn homeostasis in TMEM165-depleted cells. We show that Mn supplementation fully rescues the Mn content in the secretory pathway/organelles of TMEM165-depleted cells and hence the glycosylation process. Strong cytosolic and organellar Mn accumulations can also be observed in TMEM165- and SPCA1-depleted cells upon incubation with increasing Mn concentrations, thus demonstrating the crucial involvement of these two proteins in cellular Mn homeostasis. Interestingly, our results show that the cellular Mn homeostasis maintenance in control cells is correlated with the presence of TMEM165 and that the Mn-detoxifying capacities of cells, through the activity of SPCA1, rely on the Mn-induced degradation mechanism of TMEM165. Finally, this paper highlights that TMEM165 is essential in secretory pathway/organelles Mn homeostasis maintenance to ensure both Golgi glycosylation enzyme activities and cytosolic Mn detoxification.Show less >
Language :
Anglais
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
Université de Lille
CNRS
CNRS
Collections :
Research team(s) :
Mécanismes moléculaires de la N-glycosylation et pathologies associées
Submission date :
2023-07-19T08:22:46Z
2023-09-08T09:17:10Z
2023-09-08T09:17:10Z
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