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Vascular Biology

A Novel mRNA Binding Protein Complex Promotes Localized Plasminogen Activator Inhibitor-1 Accumulation at the Myoendothelial Junction

Katherine R. Heberlein, Jenny Han, Adam C. Straub, Angela K. Best, Christoph Kaun, Johann Wojta, Brant E. Isakson
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https://doi.org/10.1161/ATVBAHA.112.246371
Arteriosclerosis, Thrombosis, and Vascular Biology. 2012;ATVBAHA.112.246371
Originally published March 1, 2012
Katherine R. Heberlein
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Jenny Han
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Adam C. Straub
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Angela K. Best
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Christoph Kaun
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Johann Wojta
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Brant E. Isakson
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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.

Methods and 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.

Conclusion—We conclude that PAI-1 can be locally translated at the MEJ due to a unique mRNA binding protein complex.

  • plasminogen activators
  • NAMPT
  • SERBP1
  • myoendothelial junctions
  • Staufen
  • Received October 28, 2011.
  • Accepted February 20, 2012.
  • © 2012 American Heart Association, Inc.
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    A Novel mRNA Binding Protein Complex Promotes Localized Plasminogen Activator Inhibitor-1 Accumulation at the Myoendothelial Junction
    Katherine R. Heberlein, Jenny Han, Adam C. Straub, Angela K. Best, Christoph Kaun, Johann Wojta and Brant E. Isakson
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2012;ATVBAHA.112.246371, originally published March 1, 2012
    https://doi.org/10.1161/ATVBAHA.112.246371

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    A Novel mRNA Binding Protein Complex Promotes Localized Plasminogen Activator Inhibitor-1 Accumulation at the Myoendothelial Junction
    Katherine R. Heberlein, Jenny Han, Adam C. Straub, Angela K. Best, Christoph Kaun, Johann Wojta and Brant E. Isakson
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2012;ATVBAHA.112.246371, originally published March 1, 2012
    https://doi.org/10.1161/ATVBAHA.112.246371
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