PPFIA1 drives active α5β1 integrin recycling and controls fibronectin fibrillogenesis and vascular morphogenesis



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.

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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
Depositing User: Symplectic Admin
Date Deposited: 17 Nov 2016 14:24
Last Modified: 20 Jan 2022 13:10
DOI: 10.1038/ncomms13546
Open Access URL: http://www.nature.com/articles/ncomms13546
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3004569