Unknown

Dataset Information

0

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


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.

SUBMITTER: Mana G 

PROVIDER: S-EPMC5122980 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC7005302 | biostudies-literature
| S-EPMC6063507 | biostudies-literature
2022-08-09 | PXD031508 | Pride
2020-02-11 | GSE94590 | GEO
| S-EPMC3131929 | biostudies-literature
| S-EPMC4252364 | biostudies-literature
| S-EPMC7316217 | biostudies-literature
| S-EPMC7734169 | biostudies-literature
| S-EPMC3833817 | biostudies-literature
| S-EPMC4728102 | biostudies-literature