| First Author | Mana G | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 13546 | PubMed ID | 27876801 |
| Mgi Jnum | J:243070 | Mgi Id | MGI:5907562 |
| Doi | 10.1038/ncomms13546 | Citation | Mana G, et al. (2016) PPFIA1 drives active alpha5beta1 integrin recycling and controls fibronectin fibrillogenesis and vascular morphogenesis. Nat Commun 7:13546 |
| abstractText | Basolateral polymerization of cellular fibronectin (FN) into a meshwork drives endothelial cell (EC) polarity and vascular remodelling. However, mechanisms coordinating alpha5beta1 integrin-mediated extracellular FN endocytosis and exocytosis of newly synthesized FN remain elusive. Here we show that, on Rab21-elicited internalization, FN-bound/active alpha5beta1 is recycled to the EC surface. We identify a pathway, comprising the regulators of post-Golgi carrier formation PI4KB and AP-1A, the small GTPase Rab11B, the surface tyrosine phosphatase receptor PTPRF and its adaptor PPFIA1, which we propose acts as a funnel combining FN secretion and recycling of active alpha5beta1 integrin from the trans-Golgi network (TGN) to the EC surface, thus allowing FN fibrillogenesis. In this framework, PPFIA1 interacts with active alpha5beta1 integrin and localizes close to EC adhesions where post-Golgi carriers are targeted. We show that PPFIA1 is required for FN polymerization-dependent vascular morphogenesis, both in vitro and in the developing zebrafish embryo. |
