FRMPD4, also called PDZ domain-containing protein 10 (PDZD10), PDZK10, or PSD-95-interacting regulator of spine morphogenesis (Preso), is a novel PSD-95-interacting FERM and PDZ domain protein that regulates dendritic spine morphogenesis. It acts as a positive regulator of dendritic spine morphogenesis and density. It is required for the maintenance of excitatory synaptic transmission. It binds phosphatidylinositol 4,5-bisphosphate. FRMPD4 contains WW, PDZ and FERM domains in the N-terminal region. This entry corresponds to a conserved region in the C-terminal region of FRMPD4 that binds to tetratricopeptide (TPR) repeats present in the N-terminal domain of adaptor protein LGN. LGN plays a crucial role in mitotic spindle orientation and cell polarization via interaction with multiple targets including FRMPD4 [, ].
FRMPD1, FRMPD3, and FRMPD4 contain an N-terminal PDZ domain and a C-terminal FERM domain. The PDZ domain helps anchor transmembrane proteins to the cytoskeleton and hold together signaling complexes. The PDZ domain also binds to a short region of the C terminus of other specific proteins. The FERM domain is composed of three subdomains: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3), which form a clover leaf fold. The C-lobe/F3 within the FERM domain is part of the PH domain superfamily. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs) , the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites [, ].This entry represents the C-lobe of the FERM domain found in FRMPD1/3/4. FRMPD1 regulates the subcellular location of activator of G-protein signaling 3 and its interaction with G-proteins []. FRMPD4 has been shown to regulates dendritic spine morphogenesis []. The function of FRMPD3 is not clear.
FAK1 (focal adhesion kinase 1) is a non-receptor tyrosine kinase that localises to focal adhesions in adherent cells and it is involved in diverse cellular roles. The N-terminal region of FAK1 contains a FERM domain which is subdivided FERM_N or A-lobe, FERM_M or B-lobe and FERM_C or C-lobe. This entry represents the C-lobe, which is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites [, , , , ]. This domain is also present in protein-tyrosine kinase 2-beta (also known as PYK2), a cytoplasmic, non-receptor tyrosine kinase which is a close paralogue to FAK in vertebrates. FRMPD1/3/4 also contain this domain; FRMPD1 regulates the subcellular location of activator of G-protein signalling 3 and its interaction with G-proteins. FRMPD4 has been shown to regulate dendritic spine morphogenesis and the function of FRMPD3 is not clear.
