The Novel Rab11-FIP/Rip/RCP Family of Proteins Displays Extensive Homo- and Hetero-Interacting Abilities

Wallace, Deborah; Lindsay, Andrew J.; Hendrick, Alan G.; McCaffrey, Mary W.

doi:10.1006/bbrc.2002.6736

Cited by 79 publications

(87 citation statements)

References 22 publications

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“…Rab11 and Arf5/6 bind to C-terminal end and C-terminal half of the coiled-coil domain, respectively (Prekeris et al, 2001;Shiba et al, 2006;Schonteich et al, 2007). The domain also mediates homodimerization and heterodimer formation with other FIPs, which also contain coiled-coil domain in their C-terminal region (Wallace et al, 2002;Eathiraj et al, 2006;Shiba et al, 2006;Horgan et al, 2007). We found the ASAP1 BAR domain binds to the middle of the FIP3 coiled-coil domain.…”

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confidence: 72%

Arf GTPase-activating Protein ASAP1 Interacts with Rab11 Effector FIP3 and Regulates Pericentrosomal Localization of Transferrin Receptor–positive Recycling Endosome

Inoue

Prekeris

et al. 2008

MBoC

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ADP-ribosylation factors (Arfs) and Arf GTPase-activating proteins (GAPs) are key regulators of membrane trafficking and the actin cytoskeleton. The Arf GAP ASAP1 contains an N-terminal BAR domain, which can induce membrane tubulation. Here, we report that the BAR domain of ASAP1 can also function as a protein binding site. Two-hybrid screening identified FIP3, which is a putative Arf6-and Rab11-effector, as a candidate ASAP1 BAR domain-binding protein. Both coimmunoprecipitation and in vitro pulldown assays confirmed that ASAP1 directly binds to FIP3 through its BAR domain. ASAP1 formed a ternary complex with Rab11 through FIP3. FIP3 binding to the BAR domain stimulated ASAP1 GAP activity against Arf1, but not Arf6. ASAP1 colocalized with FIP3 in the pericentrosomal endocytic recycling compartment. Depletion of ASAP1 or FIP3 by small interfering RNA changed the localization of transferrin receptor, which is a marker of the recycling endosome, in HeLa cells. The depletion also altered the trafficking of endocytosed transferrin. These results support the conclusion that ASAP1, like FIP3, functions as a component of the endocytic recycling compartment. INTRODUCTIONArf family GTP-binding proteins and their GTPase-activating proteins (Arf GAPs) play crucial roles for membrane traffic and actin remodeling (D'Souza-Schorey and Chavrier, 2006;Gillingham and Munro, 2007). Arf GAPs share the same catalytic domain, the Arf GAP domain, which is responsible for GTP hydrolysis. In humans, 31 genes encoding proteins with Arf GAP domains have been found. They are classified into several subfamilies based on their domain structures Inoue and Randazzo, 2007). Three subfamilies, ArfGAPs, SMAPs, and GITs, have an Arf GAP domain at the N-terminus of the molecules. In contrast, the others, which are called AZAP-family Arf GAPs, contain an Arf GAP domain following a pleckstrin homology (PH) domain in the middle of the protein. They are subdivided into four subfamilies, ASAPs, ACAPs, ARAPs, and AGAPs.ASAP1 is one of the best-characterized Arf GAPs. In addition to PH and Arf GAP domains, ASAP1 contains an N-terminal Bin, Amphiphysin, and Rvs167/Rvs161 (BAR) domain and, in the C-terminal half of the protein, a proline (Pro)-rich domain and Src homology 3 (SH3) domain. Other ASAP isoforms, ASAP2 and ASAP3, have similar domain structures and high homology, especially in the Arf GAP domains, although ASAP3 lacks C-terminal SH3 domain (Ha et al., 2008). Through its Pro-rich and SH3 domains, ASAP1 interacts with a number of proteins, which are mainly adhesion-and actin cytoskeleton-related proteins including Src, focal adhesion kinase (FAK), Crk/CrkL, and cortactin (Brown et al., 1998;Liu et al., 2002;Oda et al., 2003;Onodera et al., 2005;Bharti et al., 2007). ASAP1 is a component of three integrated membrane/actin cytoskeleton structures: focal adhesions, circular dorsal ruffles (CDRs) and invadopodia/podosomes. ASAP1 associates with focal adhesions in fibroblasts . The focal adhesion localization depends on the interaction of ASAP1 with FA...

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confidence: 72%

Arf GTPase-activating Protein ASAP1 Interacts with Rab11 Effector FIP3 and Regulates Pericentrosomal Localization of Transferrin Receptor–positive Recycling Endosome

Inoue

Prekeris

et al. 2008

MBoC

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“…Divalent effectors that interact with two Rab proteins may act as the connectors between subdomains (51). Such effectors have been described for Rab4 and Rab11 (54), and more combinations may arise from the hetero-dimerization of certain effectors (55). The Rab11(S29F) compartment remains accessible to Tf and no fusion of the EEA1 and Rab11 membranes is observed, indicating that the communication mediated by connecting effectors is not fully impaired by this mutant.…”

Section: Mutations In the Novel Site Promote Morphological And Functimentioning

confidence: 90%

The Structural GDP/GTP Cycle of Rab11 Reveals a Novel Interface Involved in the Dynamics of Recycling Endosomes

Pasqualato

Senic-Matuglia²,

Renault³

et al. 2004

Journal of Biological Chemistry

105

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The small GTP-binding protein Rab11 is an essential regulator of the dynamics of recycling endosomes. Here we report the crystallographic analysis of the GDP/GTP cycle of human Rab11a, and a structure-based mutagenesis study that identifies a novel mutant phenotype. The crystal structures show that the nucleotide-sensitive switch 1 and 2 regions differ from those of other Rab proteins. In Rab11-GDP, they contribute to a close packed symmetrical dimer, which may associate to membranes in the cell and allow Rab11 to undergo GDP/ GTP cycles without recycling to the cytosol. The structure of active Rab11 delineates a three-dimensional site that includes switch 1 and is separate from the site defined by the Rab3/Rabphilin interface. It is proposed to form a novel interface for a Rab11 partner compatible with the simultaneous binding of another partner at the Rabphilin interface. Mutation of Ser 29 to Phe in this epitope resulted in morphological modifications of the recycling compartment that are distinct from those induced by the classical dominant-negative and constitutively active Rab11 mutants. Recycling endosomes condensed in the perinuclear region where they retained recycling transferrin, and they clustered Rab11-and EEA1-positive membranes. Altogether, our study suggests that this mutation impairs a specific subset of Rab11 interactions, possibly those involved in cytoskeleton-based movements driving the slow recycling pathway.

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“…It has been previously reported that FIPs may form homodimers or even heterodimers (26). This raises an interesting possibility of cross-talk between different FIPs via heterodimerization.…”

Section: Fig 7 Mutational Analysis Of the Conserved Rbd Of Fipsmentioning

confidence: 97%

“…Homodimers-It has been previously suggested that FIPs can form homodimers and heterodimers, yet it remains unclear whether dimerization is dependent on Rab11 binding (26). To test this, we produced recombinant full-length GST-FIP fusion proteins in insect cells and truncated FIPs in E. coli and tested their ability to form homodimers or heterodimers with other FIP family member proteins in the presence or absence of Rab11a.…”

Section: Rab11 Effector Proteins (Fips) Formmentioning

confidence: 99%

Molecular Characterization of Rab11 Interactions with Members of the Family of Rab11-interacting Proteins

Junutula¹,

Schonteich

Wilson

et al. 2004

Journal of Biological Chemistry

126

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The Rab11 subfamily of GTPases plays an important role in vesicle trafficking from endosomes to the plasma membrane. At least six Rab11 effectors (family of Rab11-interacting proteins (FIPs)) have been shown to interact with Rab11 and are hypothesized to regulate various membrane trafficking pathways such as transferrin recycling, cytokinesis, and epidermal growth factor trafficking. In this study, we characterized interactions of FIPs with the Rab11 GTPase using isothermal titration calorimetric studies and mutational analysis. Our data suggest that FIPs cannot differentiate between GTPbound Rab11a and Rab11b in vitro (50 -100 nM affinity) and in vivo. We also show that, although FIPs interact with the GDP-bound form of Rab11 in vitro, the binding affinity (>1000 nM) is not sufficient for FIP and GDPbound Rab11 interactions to occur in vivo. Mutational analysis revealed that both the conserved hydrophobic patch and Tyr 628 are important for the GTP-dependent binding of Rab11 to FIPs. The entropy and enthalpy analyses suggest that binding to Rab11a/b may induce conformational changes in FIPs.

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The Novel Rab11-FIP/Rip/RCP Family of Proteins Displays Extensive Homo- and Hetero-Interacting Abilities

Cited by 79 publications

References 22 publications

Arf GTPase-activating Protein ASAP1 Interacts with Rab11 Effector FIP3 and Regulates Pericentrosomal Localization of Transferrin Receptor–positive Recycling Endosome

Arf GTPase-activating Protein ASAP1 Interacts with Rab11 Effector FIP3 and Regulates Pericentrosomal Localization of Transferrin Receptor–positive Recycling Endosome

The Structural GDP/GTP Cycle of Rab11 Reveals a Novel Interface Involved in the Dynamics of Recycling Endosomes

Molecular Characterization of Rab11 Interactions with Members of the Family of Rab11-interacting Proteins

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