mrNa Binding Protein Complex Promotes Localized Plasminogen activator inhibitor-1 accumulation at the Myoendothelial Junction

The myoendothelial junction (MEJ) is a heterocellular junction located predominantly within the resistance vasculature and comprises vascular smooth muscle cells (VSMCs) and endothelial cell (EC) extensions that extend from each cell type into the internal elastic lamina and form a close apposition with the opposing cell membrane. The MEJ is presumed to be a highly organized signaling microdomain, acting as a conduit for heterocellular signaling within the vasculature. Indeed, deregulation of the MEJ is associated with several disease states, but the mechanism for how these changes are occurring has not been fully described. Most recently, changes in the formation of MEJs were shown to be regulated by plasminogen activator inhibitor-1 (PAI-1) at the MEJ. The expression of PAI-1 directly affected MEJ formation both in vitro and in vivo, with potential effects on signaling between the 2 cell types. However, despite its importance in MEJ formation, the mechanism for PAI-1 localization to the MEJ remains undefined. Although a common means of achieving subcellular organization is through protein trafficking, recent focus has highlighted a role for localization of messenger RNA (mRNA), which suggests that the ability to localize a single transcript that acts as a template for translating several copies of the same protein may be more energy efficient for the cell. Additionally, localized protein translation can facilitate the rapid accumulation of a protein in response to various stimuli. For mRNA localization to occur, the transcript of interest is typically bound by an mRNAbinding protein (RBP), forming an mRNARBP complex, which is trafficked to the targeted area of a cell. Importantly, the mRNARBP complex must be stabilized or anchored to the cytoskeleton within the targeted area of the cell to achieve asymmetrical distribution of the protein. To test the hypothesis that PAI-1 localization to the MEJ can be achieved through localization of PAI-1 mRNA, we looked at the expression of PAI-1 as well as 2 RBPs, the PAI-1 mRNA stabilizing RBP, serpine binding protein-1 (SERBP1) and Staufen, an RBP associated with PAI-1 mRNA degradation, in response to inflammatory stimulation. We also looked at a a Novel mrNa Binding Protein Complex Promotes Localized Plasminogen activator inhibitor-1 accumulation at the Myoendothelial Junction