Candice Sartre, François Peurois, Marie Ley, Marie-Hélène Kryszke, Wenhua Zhang, Delphine Courilleau, Rodolphe Fischmeister, Yves Ambroise, Mahel Zeghouf, Sarah Cianferani, Yann Ferrandez, Jacqueline Cherfils
EPAC1, a cAMP-activated GEF for Rap GTPases, is a major transducer of cAMP signaling and a therapeutic target in cardiac diseases. The recent discovery that cAMP is compartmentalized in membrane-proximal nanodomains challenged the current model of EPAC1 activation in the cytosol. Here, we discover that anionic membranes are a major component of EPAC1 activation. We find that anionic membranes activate EPAC1 independently of cAMP, increase its affinity for cAMP by two orders of magnitude, and synergize with cAMP to yield maximal GEF activity...
July 12, 2023: Nature Communications