| First Author | Heberlein KR | Year | 2012 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 32 |
| Issue | 5 | Pages | 1271-9 |
| PubMed ID | 22383705 | Mgi Jnum | J:196928 |
| Mgi Id | MGI:5490205 | Doi | 10.1161/ATVBAHA.112.246371 |
| Citation | Heberlein KR, et al. (2012) A novel mRNA binding protein complex promotes localized plasminogen activator inhibitor-1 accumulation at the myoendothelial junction. Arterioscler Thromb Vasc Biol 32(5):1271-9 |
| abstractText | 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. METHODS AND RESULTS: We identified PAI-1 protein enrichment at the MEJ in obese mice and in response to tumor necrosis factor (TNF-alpha) with a vascular cell coculture. However, PAI-1 mRNA was also found at the MEJ and transfection with a PAI-1-GFP with TNF-alpha 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-alpha, whereas Staufen, which degrades PAI-1 mRNA, was absent in obese mice and after TNF-alpha application. We identified nicotinamide phosphoribosyl transferase as a serpine binding protein-1 binding partner with a functional tau-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. |
