ZFIN ID: ZDB-PUB-161124-16
PPFIA1 drives active α5β1 integrin recycling and controls fibronectin fibrillogenesis and vascular morphogenesis
Mana, G., Clapero, F., Panieri, E., Panero, V., Böttcher, R.T., Tseng, H.Y., Saltarin, F., Astanina, E., Wolanska, K.I., Morgan, M.R., Humphries, M.J., Santoro, M.M., Serini, G., Valdembri, D.
Date: 2016
Source: Nature communications   7: 13546 (Journal)
Registered Authors: Santoro, Massimo
Keywords: Body patterning, Integrins
MeSH Terms:
  • Adaptor Proteins, Signal Transducing/genetics
  • Adaptor Proteins, Signal Transducing/metabolism*
  • Animals
  • Cells, Cultured
  • Embryo, Nonmammalian
  • Fibronectins/genetics
  • Fibronectins/metabolism*
  • Gene Expression Regulation/physiology*
  • Golgi Apparatus/physiology
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Integrin alpha5beta1/genetics
  • Integrin alpha5beta1/metabolism*
  • Neovascularization, Physiologic/physiology
  • Zebrafish
PubMed: 27876801 Full text @ Nat. Commun.
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.