Ras-related protein Rab14 is a small GTPase that mediates endocytic recycling and functions in phagosome maturation [, ]. Rab14 and its exchange factor FAM116 regulates the specific endocytic transport of ADAM10 and thereby N-cadherin shedding and cell motility [, ]. Rab14 regulates claudin-2 trafficking, which is required for epithelial morphogenesis []. It regulates apical targeting in polarised epithelial cells []. Rab14 also regulates the interaction of phagosomes with early endocytic compartments and the maturation of macrophage phagosomes containing the fungal pathogen Candida albicans []. Drosophila Rab14 mediates phagocytosis in the immune response to Staphylococcus aureus [].
This domain is found in late secretory protein Avl9, which is required for the generation of secretory vesicles as well as for actin polarization and polarized growth. It is also found in DENND6 proteins, which act as guanine nucleotide exchange factors (GEF) for RAB14 [].
Rab GTPases recruit various effector proteins to organelles and vesicles. Rab11-family interacting proteins (FIPs) are involved in mediating the role of Rab11. FIPs can be divided into three classes: class I FIPs (Rip11/Rab11-FIP5, RCP/RAB11FIP1, and FIP2) which contain a C2 domain after N terminus of the protein, class II FIPs (FIP3 and FIP4) which contain two EF-hands and a proline rich region, and class III FIPs (FIP1) which exhibits no homology to known protein domains. All FIP proteins contain a highly conserved, 20-amino acid motif at the C terminus of the protein, known as Rab11/25 binding domain (RBD). Class I FIPs are thought to bind to endocytic membranes via their C2 domain, which interacts directly with phospholipids. Class II FIPs do not have any membrane binding domains leaving much to speculate about the mechanism involving FIP3 and FIP4 interactions with endocytic membranes []. Class I FIPs, but not the class II FIPs, also interact with Rab14 [].The exact function of the Rab11 and FIP interaction is unknown, but there is speculation that it involves the role of forming a targeting complex that recruits a group of proteins involved in membrane transport to organelles. Recent studies have identified several Rab11-FIP complex-binding proteins that regulate distinct membrane traffic pathways [].This family consist of class I FIPs.
