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Nat Commun. 2016 Nov 23;7:13546. doi: 10.1038/ncomms13546.

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

Author information

1
Department of Oncology, University of Torino School of Medicine, Candiolo, Torino 10060, Italy.
2
Laboratory of Cell Adhesion Dynamics, Candiolo Cancer Institute-Fondazione del Piemonte per l'Oncologia (FPO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Candiolo, Torino 10060, Italy.
3
Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, 10126 Torino, Italy.
4
Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried 82152, Germany.
5
Laboratory of Vascular Oncology, Candiolo Cancer Institute-Fondazione del Piemonte per l'Oncologia (FPO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Candiolo, Torino 10060, Italy.
6
Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3BX, UK.
7
Wellcome Trust Centre for Cell-Matrix Research, Faculty of Biology, Medicine &Health, University of Manchester, Manchester M13 9PT, UK.
8
Laboratory of Endothelial Molecular Biology, Vesalius Research Center, VIB, Leuven B-3000, Belgium.

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.

PMID:
27876801
PMCID:
PMC5122980
DOI:
10.1038/ncomms13546
[Indexed for MEDLINE]
Free PMC Article

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