| First Author | Rainero E | Year | 2015 |
| Journal | Cell Rep | PubMed ID | 25600874 |
| Mgi Jnum | J:222806 | Mgi Id | MGI:5645621 |
| Doi | 10.1016/j.celrep.2014.12.037 | Citation | Rainero E, et al. (2015) Ligand-Occupied Integrin Internalization Links Nutrient Signaling to Invasive Migration. Cell Rep |
| abstractText | Integrin trafficking is key to cell migration, but little is known about the spatiotemporal organization of integrin endocytosis. Here, we show that alpha5beta1 integrin undergoes tensin-dependent centripetal movement from the cell periphery to populate adhesions located under the nucleus. From here, ligand-engaged alpha5beta1 integrins are internalized under control of the Arf subfamily GTPase, Arf4, and are trafficked to nearby late endosomes/lysosomes. Suppression of centripetal movement or Arf4-dependent endocytosis disrupts flow of ligand-bound integrins to late endosomes/lysosomes and their degradation within this compartment. Arf4-dependent integrin internalization is required for proper lysosome positioning and for recruitment and activation of mTOR at this cellular subcompartment. Furthermore, nutrient depletion promotes subnuclear accumulation and endocytosis of ligand-engaged alpha5beta1 integrins via inhibition of mTORC1. This two-way regulatory interaction between mTORC1 and integrin trafficking in combination with data describing a role for tensin in invasive cell migration indicate interesting links between nutrient signaling and metastasis. |
