| First Author | Gong Y | Year | 2021 |
| Journal | Dev Cell | Volume | 56 |
| Issue | 14 | Pages | 2103-2120.e9 |
| PubMed ID | 34214490 | Mgi Jnum | J:308559 |
| Mgi Id | MGI:6730046 | Doi | 10.1016/j.devcel.2021.06.011 |
| Citation | Gong Y, et al. (2021) Vangl2 limits chaperone-mediated autophagy to balance osteogenic differentiation in mesenchymal stem cells. Dev Cell 56(14):2103-2120.e9 |
| abstractText | Lysosomes are the recycling center and nutrient signaling hub of the cell. Here, we show that lysosomes also control mesenchymal stem cell (MSC) differentiation by proteomic reprogramming. The chaperone-mediated autophagy (CMA) lysosome subgroup promotes osteogenesis, while suppressing adipogenesis, by selectively removing osteogenesis-deterring factors, especially master transcriptional factors, such as adipogenic TLE3, ZNF423, and chondrogenic SOX9. The activity of the CMA-committed lysosomes in MSCs are controlled by Van-Gogh-like 2 (Vangl2) at lysosomes. Vangl2 directly binds to lysosome-associated membrane protein 2A (LAMP-2A) and targets it for degradation. MSC-specific Vangl2 ablation in mice increases LAMP-2A expression and CMA-lysosome numbers, promoting bone formation while reducing marrow fat. The Vangl2:LAMP-2A ratio in MSCs correlates inversely with the capacity of the cells for osteoblastic differentiation in humans and mice. These findings demonstrate a critical role for lysosomes in MSC lineage acquisition and establish Vangl2-LAMP-2A signaling as a critical control mechanism. |
