PPFIA1 drives active a5b1 integrin recycling and controls fibronectin fibrillogenesis and vascular morphogenesis

Giulia Mana, fabiana caplero, Emiliano Panieri, Valentina Panero, ralph bottcher, Hui-Yuan Tseng, Federico Saltarin, Elena Astanina, Katarzyna Wolanska, Mark Morgan, martin humphries, Massimo Santoro, Guido Serini, Donatella Valdembri

Research output: Contribution to journalArticlepeer-review

Abstract

Basolateral polymerization of cellular fibronectin (FN) into a meshwork drives endothelial cell (EC) polarity and vascular remodelling. However, mechanisms coordinating a5b1 integrin-mediated extracellular FN endocytosis and exocytosis of newly synthesized FN remain elusive. Here we show that, on Rab21-elicited internalization, FN-bound/active a5b1 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 a5b1 integrin from the trans-Golgi network (TGN) to the EC surface, thus allowing FN fibrillogenesis. In this framework, PPFIA1 interacts with active a5b1 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.
Original languageEnglish
JournalNature Communications
Publication statusPublished - 2016

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