التفاصيل البيبلوغرافية
| العنوان: |
GRAMD1/ASTER‐mediated cholesterol transport promotes Smoothened cholesterylation at the endoplasmic reticulum |
| المؤلفون: |
Qiu, Zhi‐Ping, Lin, Zi‐Cun, Hu, Ao, Liu, Yuan‐Bin, Zeng, Wan‐Er, Zhao, Xiaolu, Shi, Xiong‐Jie, Luo, Jie, Song, Bao‐Liang |
| المساهمون: |
Ministry of Science and Technology of the People's Republic of China, National Natural Science Foundation of China |
| المصدر: |
The EMBO Journal ; volume 42, issue 3 ; ISSN 0261-4189 1460-2075 |
| بيانات النشر: |
Springer Science and Business Media LLC |
| سنة النشر: |
2022 |
| مصطلحات موضوعية: |
General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, Molecular Biology, General Neuroscience |
| الوصف: |
Hedgehog (Hh) signaling pathway plays a pivotal role in embryonic development. Hh binding to Patched1 (PTCH1) derepresses Smoothened (SMO), thereby activating the downstream signal transduction. Covalent SMO modification by cholesterol in its cysteine‐rich domain (CRD) is essential for SMO function. SMO cholesterylation is a calcium‐accelerated autoprocessing reaction, and STIM1‐ORAI1‐mediated store‐operated calcium entry promotes cholesterylation and activation of endosome‐localized SMO. However, it is unknown whether the Hh‐PTCH1 interplay regulates the activity of the endoplasmic reticulum (ER)‐localized SMO. Here, we found that PTCH1 inhibited the COPII‐dependent export of SMO from the ER, whereas Hh promoted this process. The RRxWxR amino acid motif in the cytosolic tail of SMO was essential for COPII recognition, ciliary localization, and signal transduction activity. Hh and PTCH1 regulated cholesterol modification of the ER‐localized SMO, and SMO cholesterylation accelerated its exit from ER. The GRAMD1/ASTER sterol transport proteins facilitated cholesterol transfer to ER from PM, resulting in increased SMO cholesterylation and enhanced Hh signaling. Collectively, we reveal a regulatory role of GRAMD‐mediated cholesterol transport in ER‐resident SMO maturation and Hh signaling. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.15252/embj.2022111513 |
| الإتاحة: |
https://doi.org/10.15252/embj.2022111513Test |
| حقوق: |
http://onlinelibrary.wiley.com/termsAndConditions#vorTest |
| رقم الانضمام: |
edsbas.2D0A0DF0 |
| قاعدة البيانات: |
BASE |
