Zdhhc1- and Zdhhc2-mediated Gpm6a palmitoylation is essential for maintenance of mammary stem cell activity
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 Cys<sup>17,18</sup> and Cys<sup>246</sup> 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.
Authors
- Luyao Guo (ORCID: https://orcid.org/0000-0001-5404-4648)
- Gaosong Wu
- Cheguo Cai (ORCID: https://orcid.org/0000-0002-3712-1696)
- Wei Wei (ORCID: https://orcid.org/0000-0001-5929-7409)
- Weizhen Chen (ORCID: https://orcid.org/0000-0003-0660-0990)
Institutions
- Wuhan University (CN)
- Zhongnan Hospital of Wuhan University (CN)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-09-01
- DOI
- https://doi.org/10.1016/j.celrep.2024.114762
- Citations
- 9
- Primary Topic
- Cancer Cells and Metastasis
- Type
- article
- Field-Weighted Citation Impact
- 2.54
Funders
- National Natural Science Foundation of China
- Chinese Academy of Sciences
- Ministry of Science and Technology of the People's Republic of China
- National University's Basic Research Foundation of China
- National Key Research and Development Program of China
- Fundamental Research Funds for the Central Universities