Background information: Rab11 and Rab14 are two related Rab GTPases that are believed to function in endosomal recycling and Golgi/endosome transport processes. We, and others, have identified a group of proteins that interact with Rab11 and function as Rab11 effectors, known as the Rab11-FIPs (family interacting proteins). This protein family has been sub-classified into two groups - class I FIPs [FIP2, RCP (Rab coupling protein) and Rip11 (Rab11-interacting protein)] and class II FIPs (FIP3 and FIP4).
Results: In the present study we identify the class I FIPs as dual Rab-binding proteins by demonstrating that they also interact with Rab14 in a GTP-dependent manner. We show that these interactions are specific for the class I FIPs and that they occur via their C-terminal regions, which encompass the previously described RBD (Rab11-binding domain). Furthermore, we show that Rab14 significantly co-localizes with the TfnR (transferrin receptor) and that Rab14 Q70L co-localizes with Rab11a and with the class I FIPs on the ERC (endosomal recycling compartment) during interphase. Additionally, we show that during cytokinesis Rab14 localizes to the cleavage furrow/midbody.
Conclusions: The data presented in the present study, which identifies the class I FIPs as the first putative effector proteins for the Rab14 GTPase, indicates greater complexity in the Rab-binding specificity of the class I FIP proteins.