<p>(A) Domain structure of Epac2: cAMP-binding (cAMP); domain found in Dishevelled, Egl-10, and Pleckstrin (DEP); N-terminus of Ras-exchanger motif (REM); Ras-association (RA); Rap-Guanine Exchange Factor (Rap-GEF). Asterisk indicates position of Epac2-G706R rare variant. (B) Representative binary images of cortical neurons expressing GFP+Epac2-WT or GFP+Epac2-G706R. (C) Sholl analysis of apical and basal dendrites reveals a significant decrease in basal complexity in Epac2-G706R-expressing cells. (D) Quantification of apical and basal dendrite length. (E) Ras activation by GTPγs results in stronger coimmunoprecipitation of Epac2 with Ras in neurons, while inactivation of Ras by GDP reduces Ras-Epac2 interaction. (F) Quantification of (E). (G) Epac2-G706R point mutation exhibits impaired interaction with Ras in hEK293 cells. (H) Quantification of G. *<i>p</i><0.05, **<i>p</i><0.01, ***<i>p</i><0.001; scale bar, 100 µm.</p
