| First Author | Kenific CM | Year | 2016 |
| Journal | J Cell Biol | Volume | 212 |
| Issue | 5 | Pages | 577-90 |
| PubMed ID | 26903539 | Mgi Jnum | J:236653 |
| Mgi Id | MGI:5806719 | Doi | 10.1083/jcb.201503075 |
| Citation | Kenific CM, et al. (2016) NBR1 enables autophagy-dependent focal adhesion turnover. J Cell Biol 212(5):577-90 |
| abstractText | Autophagy is a catabolic pathway involving the sequestration of cellular contents into a double-membrane vesicle, the autophagosome. Although recent studies have demonstrated that autophagy supports cell migration, the underlying mechanisms remain unknown. Using live-cell imaging, we uncover that autophagy promotes optimal migratory rate and facilitates the dynamic assembly and disassembly of cell-matrix focal adhesions (FAs), which is essential for efficient motility. Additionally, our studies reveal that autophagosomes associate with FAs primarily during disassembly, suggesting autophagy locally facilitates the destabilization of cell-matrix contact sites. Furthermore, we identify the selective autophagy cargo receptor neighbor of BRCA1 (NBR1) as a key mediator of autophagy-dependent FA remodeling. NBR1 depletion impairs FA turnover and decreases targeting of autophagosomes to FAs, whereas ectopic expression of autophagy-competent, but not autophagy-defective, NBR1 enhances FA disassembly and reduces FA lifetime during migration. Our findings provide mechanistic insight into how autophagy promotes migration by revealing a requirement for NBR1-mediated selective autophagy in enabling FA disassembly in motile cells. |
