The FERM and PDZ domain containing (FRMPD) protein family consists of four proteins that contain a FERM (Four-point-one, erzin, radixin, moesin) domain and at least one PDZ (PSD-95/Discs large/Zonula-occuldens-1) domain. FRMPD1 was initially identified through a yeast two-hybrid screening with Activator of G-protein signaling 3 (AGS3), a protein that acts to stabilize the GDP-bound conformation of Gai, as the bait. FRMPD1 binds to the tetratricopeptide repeat of AGS3 and stabilizes AGS3 in a membrane environment. Suppression of FRMPD1 in Cath.a-differentiated neuronal cells decreased the level of endogenous AGS3 in membrane fractions by ~50% and enhanced the inhibition of forskolin-induced increases in cAMP. Co-immunoprecipitation studies indicate that the interaction of AGS3 with FRMPD1 is mutually exclusive with the interaction of AGS3 with Gai3, suggesting that FRMPD1 may position AGS3 in the membrane where it can then interact with Galphai.
FERM and PDZ domain-containing protein 1; FERM domain-containing protein 2; RP11-263I4.1, FRMD2