SPCA1 governs the stability of TMEM165 in Hailey-Hailey disease - Université de Lille Accéder directement au contenu
Article Dans Une Revue Biochimie Année : 2020

SPCA1 governs the stability of TMEM165 in Hailey-Hailey disease


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.
Fichier principal
Vignette du fichier
S0300908420300870.pdf (7.35 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-03178791 , version 1 (22-08-2022)


Paternité - Pas d'utilisation commerciale



Anne-Sophie Roy, Snaigune Miskinyte, Anne Garat, Alain Hovnanian, Marie-Ange Krzewinski-Recchi, et al.. SPCA1 governs the stability of TMEM165 in Hailey-Hailey disease. Biochimie, 2020, Biochimie, 174, pp.159-170. ⟨10.1016/j.biochi.2020.04.017⟩. ⟨hal-03178791⟩
56 Consultations
12 Téléchargements



Gmail Facebook X LinkedIn More