HKUST Elucidates How IGF2’s Secretory Pathway Mediates Muscle Stem Cell Differentiation Laying Foundation for Treating Multiple Diseases
Insulin-like growth factor 2 (IGF2) plays a crucial role in skeletal myogenesis during development. While the mechanisms governing IGF2 expression and its signaling pathway have been extensively studied, how IGF2 proteins are secreted and perform their functions after synthesis is not well understood. In this study, Prof. Zhenguo Wuand Prof. Yusong Guo’sresearch teams in collaboration with researchers from Hong Kong Polytechnic University (PolyU) demonstrate that a receptor called transmembrane emp24 domain-containing protein 10 (TMED10) facilitates the export of IGF2 from the endoplasmic reticulum (ER). TMED10 recognizes an export signal on IGF2 and promotes its transport from the ER to the Golgi apparatus. Additionally, TMED10 is involved in the ER export of sortilin, a protein that regulates the export of IGF2 from the trans-Golgi network.
This finding offers potential therapeutic strategies to inhibit IGF2 secretion and downregulate its signaling, which is associated with various growth disorders.
Tiantian Li,, Feng Yang, Youshan Heng, Shaopu Zhou, Gang Wang, Jianying Wang, Jinhui Wang, Xianwei Chen, Zhong- Ping Yao, Zhenguo Wu, and Yusong Guo. TMED10 mediates the trafficking of insulin- like growth factor 2 along the secretory pathway for myoblast differentiation. PNAS 2023 Vol. 120 No. 46 e2215285120 https://doi.org/10.1073/pnas.2215285120