Distinct functions for Rap1 signaling in vascular morphogenesis and dysfunction

Rap1 signaling is important for both major processes of vessel formation: vasculogenesis, or de novo vessel formation, and angiogenesis, sprouting of new vessels from pre-existing ones. We provide an overview of genetic studies in mice and zebrafish and discuss some of the proposed underlying mechanisms derived from cellular models, with particular emphasis on Rap1’s role in angiogenesis, maintenance of endothelial barrier and connection with cerebral cavernous malformation (CCM), a neurological deficit that leads to seizures and lethal stroke. Lastly, we provide a brief summary of studies in cardiac and smooth muscle cells, where the Epac-Rap1 signaling axis is emerging as an important regulator of contractility.