title: A novel mRNA binding protein complex promotes localized plasminogen activator inhibitor-1 accumulation at the myoendothelial junction.
abstract: OBJECTIVE
  Plasminogen activator inhibitor-1 (PAI-1) has previously been shown to be key to the formation of myoendothelial junctions (MEJs) in normal and pathological states (eg, obesity). We therefore sought to identify the mechanism whereby PAI-1 could be selectively accumulated at the MEJ.
  
  
  RESULTS
  We identified PAI-1 protein enrichment at the MEJ in obese mice and in response to tumor necrosis factor (TNF-α) with a vascular cell coculture. However, PAI-1 mRNA was also found at the MEJ and transfection with a PAI-1-GFP with TNF-α did not demonstrate trafficking of the protein to the MEJ. We therefore hypothesized the PAI-1 mRNA was being locally translated and identified serpine binding protein-1, which stabilizes PAI-1 mRNA, as being enriched in obese mice and after treatment with TNF-α, whereas Staufen, which degrades PAI-1 mRNA, was absent in obese mice and after TNF-α application. We identified nicotinamide phosphoribosyl transferase as a serpine binding protein-1 binding partner with a functional τ-like microtubule binding domain. Application of peptides against the microtubule binding domain significantly decreased the number of MEJs and the amount of PAI-1 at the MEJ.
  
  
  CONCLUSIONS
  We conclude that PAI-1 can be locally translated at the MEJ as a result of a unique mRNA binding protein complex.
authors.affiliation: Robert M. Berne Cardiovascular Research Center, Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Heberlein
authors.forename: Jenny
authors.initials: J
authors.lastname: Han
authors.forename: Adam C
authors.initials: AC
authors.lastname: Straub
authors.forename: Angela K
authors.initials: AK
authors.lastname: Best
authors.forename: Christoph
authors.initials: C
authors.lastname: Kaun
authors.forename: Johann
authors.initials: J
authors.lastname: Wojta
authors.forename: Brant E
authors.initials: BE
authors.lastname: Isakson
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D005786:Gene Expression Regulation; D007365:Intercellular Junctions; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D046529:Microscopy, Electron, Transmission; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D016601:RNA-Binding Proteins