PSEN1/PEN-2 and NCT/APH1A dimers preferentially exit the ER through distinct Sec24 paralog requirements. (A) Scheme of COPII budding. Representative Western blot of COPII vesicles with different efficiencies of Sec24 isoforms A, C, and D in packaging NCT and FL PSEN1 in MEF WT, APH-tKO, and PEN-2-KO SICs. Ribophorin was a negative control, and ERGIC-53/p58 and RER1p were positive controls (filled arrowheads: immature NCT; white arrowheads: FL PSEN1; asterisks: aspecific band). (B) Quantification of A. NCT was preferentially sorted through Sec24C/D isoforms, whereas FL PSEN1 favored the Sec24A isoform. Data are presented as mean ± SEM (n = 3 or 4). NCTimm, immature NCT.