SPCA1 governs the stability of TMEM165 in ...
Document type :
Article dans une revue scientifique
Permalink :
Title :
SPCA1 governs the stability of TMEM165 in Hailey-Hailey disease
Author(s) :
Roy, Anne-Sophie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Miskinyte, Snaigune [Auteur]
Genetic skin diseases : from disease mechanism to therapies [Equipe Inserm U1163]
Garat, Anne [Auteur]
Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS]
Hovnanian, Alain [Auteur]
Genetic skin diseases : from disease mechanism to therapies [Equipe Inserm U1163]
Krzewinski, Marie-Ange [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Foulquier, Francois [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Miskinyte, Snaigune [Auteur]
Genetic skin diseases : from disease mechanism to therapies [Equipe Inserm U1163]
Garat, Anne [Auteur]

Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS]
Hovnanian, Alain [Auteur]
Genetic skin diseases : from disease mechanism to therapies [Equipe Inserm U1163]
Krzewinski, Marie-Ange [Auteur]

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

Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Journal title :
Biochimie
Volume number :
174
Pages :
159-170
Publisher :
Elsevier BV
Publication date :
2020-07
ISSN :
0300-9084
English keyword(s) :
SPCA1
Hailey-Hailey disease
TMEM165
Manganese sensitivity
Golgi
Hailey-Hailey disease
TMEM165
Manganese sensitivity
Golgi
HAL domain(s) :
Sciences du Vivant [q-bio]
Chimie/Chimie théorique et/ou physique
Chimie/Chimie théorique et/ou physique
English abstract : [en]
TMEM165 is a Golgi protein whose deficiency causes a Congenital Disorder of Glycosylation (CDG). We have demonstrated that Mn2+ supplementation could suppress the glycosylation defects observed in TMEM165-deficient cells ...
Show more >TMEM165 is a Golgi protein whose deficiency causes a Congenital Disorder of Glycosylation (CDG). We have demonstrated that Mn2+ supplementation could suppress the glycosylation defects observed in TMEM165-deficient cells and that TMEM165 was a Mn2+-sensitive protein. In the Golgi, the other transmembrane protein capable to regulate Mn2+/Ca2+ homeostasis is SPCA1, encoded by the ATP2C1 gene. A loss of one copy of the ATP2C1 gene leads to Hailey-Hailey Disease (HHD), an acantholytic skin disorder in Humans. Our latest results suggest an unexpected functional link between SPCA1 and TMEM165. In order to clarify this link in case of partial SPCA1 deficiency, HHD fibroblasts were used to assess TMEM165 expression, subcellular localization and Mn2+-induced degradation. No differences were observed regarding TMEM165 expression and localization in HHD patients’ fibroblasts compared to control fibroblasts. Nevertheless, we demonstrated both for fibroblasts and keratinocytes that TMEM165 expression is more sensitive to MnCl2 exposure in HHD cells than in control cells. We linked, using ICP-MS and GPP130 as a Golgi Mn2+ sensor, this higher Mn2+-induced sensitivity to a cytosolic Mn accumulation in MnCl2 supplemented HHD fibroblasts. Altogether, these results link the function of SPCA1 to the stability of TMEM165 in a pathological context of Hailey-Hailey disease.Show less >
Show more >TMEM165 is a Golgi protein whose deficiency causes a Congenital Disorder of Glycosylation (CDG). We have demonstrated that Mn2+ supplementation could suppress the glycosylation defects observed in TMEM165-deficient cells and that TMEM165 was a Mn2+-sensitive protein. In the Golgi, the other transmembrane protein capable to regulate Mn2+/Ca2+ homeostasis is SPCA1, encoded by the ATP2C1 gene. A loss of one copy of the ATP2C1 gene leads to Hailey-Hailey Disease (HHD), an acantholytic skin disorder in Humans. Our latest results suggest an unexpected functional link between SPCA1 and TMEM165. In order to clarify this link in case of partial SPCA1 deficiency, HHD fibroblasts were used to assess TMEM165 expression, subcellular localization and Mn2+-induced degradation. No differences were observed regarding TMEM165 expression and localization in HHD patients’ fibroblasts compared to control fibroblasts. Nevertheless, we demonstrated both for fibroblasts and keratinocytes that TMEM165 expression is more sensitive to MnCl2 exposure in HHD cells than in control cells. We linked, using ICP-MS and GPP130 as a Golgi Mn2+ sensor, this higher Mn2+-induced sensitivity to a cytosolic Mn accumulation in MnCl2 supplemented HHD fibroblasts. Altogether, these results link the function of SPCA1 to the stability of TMEM165 in a pathological context of Hailey-Hailey disease.Show less >
Language :
Anglais
Peer reviewed article :
Oui
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 :
2021-03-23T15:03:15Z
2021-03-24T07:22:10Z
2021-06-16T08:25:46Z
2021-03-24T07:22:10Z
2021-06-16T08:25:46Z
Files
- P20.58 SPCA1.pdf
- Version éditeur
- Confidential access
- Access the document