Zdhhc1- and Zdhhc2-mediated Gpm6a palmitoylation is essential for maintenance of mammary stem cell activity.
Cell Rep
; 43(9): 114762, 2024 09 24.
Article
in En
| MEDLINE
| ID: mdl-39321020
ABSTRACT
Adult mammary stem cells (aMaSCs) are vital to tissue expansion and remodeling during the process of postnatal mammary development. The protein C receptor (Procr) is one of the well-identified surface markers of multipotent aMaSCs. However, an understanding of the regulatory mechanisms governing Procr's protein stability remains incomplete. In this study, we identified Glycoprotein m6a (Gpm6a) as a critical protein for aMaSC activity modulation by using the Gpm6a knockout mouse model. Interestingly, we determined that Gpm6a depletion results in a reduction of Procr protein stability. Mechanistically, Gpm6a regulates Procr protein stability by mediating the formation of lipid rafts, a process requiring Zdhhc1 and Zdhhc2 to palmitate Gpm6a at Cys17,18 and Cys246 sites. Our findings highlight an important mechanism involving Zdhhc1- and Zdhhc2-mediated Gpm6a palmitoylation for the regulation of Procr stability, aMaSC activity, and postnatal mammary development.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Acyltransferases
/
Lipoylation
/
Mammary Glands, Animal
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Cell Rep
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Estados Unidos