High impact information on RAB11FIP2

• The results presented herein promote a coordinated role for EHD proteins and Rab11-FIP2 in mediating endocytic recycling and provide evidence for the function of EHD3 in early endosome to ERC transport [1].
• These results are consistent with a coordinated role for EHD1 and Rab11-FIP2 in regulating exit from the ERC [1].
• Rab11a, myosin Vb, and the Rab11-family interacting protein 2 (FIP2) regulate plasma membrane recycling in epithelial cells [2].
• These results indicate that phosphorylation of Rab11-FIP2 on serine 227 by MARK2 regulates an alternative pathway modulating the establishment of epithelial polarity [2].
• Analysis of these cell lines demonstrates a new role for Rab11-FIP2 in addition to that in the plasma membrane recycling system [2].

Biological context of RAB11FIP2

• In vitro association assays and co-transfection experiments in both MDCK and HeLa cells confirmed this result but further refined the binding site to amino acids 129-290 of Rab11-FIP2 [3].
• We also showed that the Rab11-FIP2 coiled-coil domain forms a parallel homodimer in solution using cross-linking and mutagenesis and sedimentation equilibrium experiments [4].
• Here we show that Rab11-FIP2 may also be involved with the process of receptor-mediated endocytosis [5].

Anatomical context of RAB11FIP2

• Expression of a deletion mutant of Rab11-FIP2, containing the RBD, caused tubulation of a transferrin receptor-positive early endosomal compartment in HeLa cells [6].
• Rab11-FIP2 functions in transferrin recycling and associates with endosomal membranes via its COOH-terminal domain [6].
• Like myosin Vb, functional studies indicated that Rab11-FIP2 is also important for normal plasma membrane recycling [3].
• We also show that Rab11-FIP2 associates with the alpha-adaptin subunit of AP-2 complexes, which are known to recruit receptors into clathrin-coated vesicles [5].

Associations of RAB11FIP2 with chemical compounds

• Green fluorescent protein-Rab11-FIP2 (129-512), which lacks its amino-terminal C2 domain, functioned as a dominant negative acting truncation that caused accumulation of Rab11a and disrupted IgA trafficking in MDCK cells and transferrin trafficking in HeLa cells [3].
• We have found that gastric microsomal membrane extracts phosphorylate Rab11-FIP2 on serine 227 [2].

Physical interactions of RAB11FIP2

• Rab11-FIP2 also interacted with dominant negative Rab11a (Rab11aS25N) and the tail of myosin Vb [7].
• Molecular dissection of Rab11 binding from coiled-coil formation in the Rab11-FIP2 C-terminal domain [4].

Other interactions of RAB11FIP2

• Using yeast two-hybrid binary screens, we demonstrated that dominant active Rab25S21V fails to interact with myosin Vb, but does interact with Rab11-FIP2 [8].
• CXCR2 recycling was also reduced by the expression Rab11-FIP2 (129-512) [9].
• A number of proteins that interact directly with Rab11-FIP2, in addition to Rab11, have been identified [10].
• It is hypothesized that Rab11-FIP2 functions to transport cargo, such as chemokine receptors and the EGF receptor, from the endocytic recycling compartment (ERC) to the plasma membrane [10].

Analytical, diagnostic and therapeutic context of RAB11FIP2

• Immunofluorescence studies indicated a colocalization of endogenous Rab11-FIP2 with green fluorescent protein-myosin Vb tail overexpressed in Madin-Darby canine kidney (MDCK) cells [3].
• Yeast two hybrid assays showed that amino acids 129-356 of Rab11-FIP2 were important for binding to myosin Vb tail [3].
• Various constructs representing the C-terminal domain of Rab11-FIP2 were characterized by circular dichroism, and their affinity with Rab11 was measured using isothermal titration calorimetry [4].
• Purification, crystallization and preliminary X-ray diffraction studies of Rab11 in complex with Rab11-FIP2 [11].

References