Mana, G, Clapero, F, Panieri, E, Panero, V, Böttcher, RT, Tseng, H-Y, Saltarin, F, Astanina, E, Wolanska, KI, Morgan, MR 
ORCID: 0000-0001-7728-9883 et al (show 4 more authors)
(2016)
PPFIA1 drives active α5β1 integrin recycling and controls fibronectin fibrillogenesis and vascular morphogenesis.
Nature Communications, 7 (1).
13546-.
Abstract
Basolateral polymerization of cellular fibronectin (FN) into a meshwork drives endothelial cell (EC) polarity and vascular remodelling. However, mechanisms coordinating α5β1 integrin-mediated extracellular FN endocytosis and exocytosis of newly synthesized FN remain elusive. Here we show that, on Rab21-elicited internalization, FN-bound/active α5β1 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 α5β1 integrin from the trans-Golgi network (TGN) to the EC surface, thus allowing FN fibrillogenesis. In this framework, PPFIA1 interacts with active α5β1 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Cells, Cultured, Golgi Apparatus, Embryo, Nonmammalian, Animals, Zebrafish, Humans, Adaptor Proteins, Signal Transducing, Fibronectins, Integrin alpha5beta1, Gene Expression Regulation, Neovascularization, Physiologic, Human Umbilical Vein Endothelial Cells |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 17 Nov 2016 14:24 |
| Last Modified: | 19 Jan 2023 07:25 |
| DOI: | 10.1038/ncomms13546 |
| Open Access URL: | http://www.nature.com/articles/ncomms13546 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3004569 |
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