Daniela I Staquicini, Marina Cardó-Vila, Jimmy A Rotolo, Fernanda I Staquicini, Fenny H F Tang, Tracey L Smith, Aditya Ganju, Carmine Schiavone, Prashant Dogra, Zhihui Wang, Vittorio Cristini, Ricardo J Giordano, Michael G Ozawa, Wouter H P Driessen, Bettina Proneth, Glauco R Souza, Lina M Brinker, Achraf Noureddine, Ashley J Snider, Daniel Canals, Juri G Gelovani, Irina Petrache, Rubin M Tuder, Lina M Obeid, Yusuf A Hannun, Richard N Kolesnick, C Jeffrey Brinker, Renata Pasqualini, Wadih Arap
The vascular endothelium from individual organs is functionally specialized, and it displays a unique set of accessible molecular targets. These serve as endothelial cell receptors to affinity ligands. To date, all identified vascular receptors have been proteins. Here, we show that an endothelial lung-homing peptide (CGSPGWVRC) interacts with C16-ceramide, a bioactive sphingolipid that mediates several biological functions. Upon binding to cell surfaces, CGSPGWVRC triggers ceramide-rich platform formation, activates acid sphingomyelinase and ceramide production, without the associated downstream apoptotic signaling...
August 22, 2023: Proceedings of the National Academy of Sciences of the United States of America