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EMBO J
2009 Feb 04;283:183-92. doi: 10.1038/emboj.2008.267.
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Ciliary targeting motif VxPx directs assembly of a trafficking module through Arf4.
Mazelova J, Astuto-Gribble L, Inoue H, Tam BM, Schonteich E, Prekeris R, Moritz OL, Randazzo PA, Deretic D.
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Dysfunctions of primary cilia and cilia-derived sensory organelles underlie a multitude of human disorders, including retinal degeneration, yet membrane targeting to the cilium remains poorly understood. Here, we show that the newly identified ciliary targeting VxPx motif present in rhodopsin binds the small GTPase Arf4 and regulates its association with the trans-Golgi network (TGN), which is the site of assembly and function of a ciliary targeting complex. This complex is comprised of two small GTPases, Arf4 and Rab11, the Rab11/Arf effector FIP3, and the Arf GTPase-activating protein ASAP1. ASAP1 mediates GTP hydrolysis on Arf4 and functions as an Arf4 effector that regulates budding of post-TGN carriers, along with FIP3 and Rab11. The Arf4 mutant I46D, impaired in ASAP1-mediated GTP hydrolysis, causes aberrant rhodopsin trafficking and cytoskeletal and morphological defects resulting in retinal degeneration in transgenic animals. As the VxPx motif is present in other ciliary membrane proteins, the Arf4-based targeting complex is most likely a part of conserved machinery involved in the selection and packaging of the cargo destined for delivery to the cilium.
Beronja,
Essential function of Drosophila Sec6 in apical exocytosis of epithelial photoreceptor cells.
2005, Pubmed
Beronja,
Essential function of Drosophila Sec6 in apical exocytosis of epithelial photoreceptor cells.
2005,
Pubmed Berson,
Disease progression in patients with dominant retinitis pigmentosa and rhodopsin mutations.
2002,
Pubmed Brown,
ASAP1, a phospholipid-dependent arf GTPase-activating protein that associates with and is phosphorylated by Src.
1998,
Pubmed Burguete,
Rab and Arl GTPase family members cooperate in the localization of the golgin GCC185.
2008,
Pubmed Chen,
Rab11 is required for trans-golgi network-to-plasma membrane transport and a preferential target for GDP dissociation inhibitor.
1998,
Pubmed Christensen,
Sensory cilia and integration of signal transduction in human health and disease.
2007,
Pubmed Corbit,
Vertebrate Smoothened functions at the primary cilium.
2005,
Pubmed de Graaf,
Phosphatidylinositol 4-kinasebeta is critical for functional association of rab11 with the Golgi complex.
2004,
Pubmed Deretic,
Phosphoinositides, ezrin/moesin, and rac1 regulate fusion of rhodopsin transport carriers in retinal photoreceptors.
2004,
Pubmed Deretic,
Regulation of sorting and post-Golgi trafficking of rhodopsin by its C-terminal sequence QVS(A)PA.
1998,
Pubmed Deretic,
Rhodopsin C terminus, the site of mutations causing retinal disease, regulates trafficking by binding to ADP-ribosylation factor 4 (ARF4).
2005,
Pubmed Deretic,
Cytoplasmic domain of rhodopsin is essential for post-Golgi vesicle formation in a retinal cell-free system.
1996,
Pubmed Deretic,
rab8 in retinal photoreceptors may participate in rhodopsin transport and in rod outer segment disk morphogenesis.
1995,
Pubmed Deretic,
Rab6 is associated with a compartment that transports rhodopsin from the trans-Golgi to the site of rod outer segment disk formation in frog retinal photoreceptors.
1993,
Pubmed Deretic,
Polarized sorting of rhodopsin on post-Golgi membranes in frog retinal photoreceptor cells.
1991,
Pubmed Deretic,
A role for rhodopsin in a signal transduction cascade that regulates membrane trafficking and photoreceptor polarity.
2006,
Pubmed D'Souza-Schorey,
ARF proteins: roles in membrane traffic and beyond.
2006,
Pubmed Eathiraj,
Structural basis for Rab11-mediated recruitment of FIP3 to recycling endosomes.
2006,
Pubmed Fielding,
Rab11-FIP3 and FIP4 interact with Arf6 and the exocyst to control membrane traffic in cytokinesis.
2005,
Pubmed Fliegauf,
When cilia go bad: cilia defects and ciliopathies.
2007,
Pubmed Geng,
Polycystin-2 traffics to cilia independently of polycystin-1 by using an N-terminal RVxP motif.
2006,
Pubmed Gillingham,
The small G proteins of the Arf family and their regulators.
2007,
Pubmed Green,
Characterization of rhodopsin mis-sorting and constitutive activation in a transgenic rat model of retinitis pigmentosa.
2000,
Pubmed Grosshans,
Rabs and their effectors: achieving specificity in membrane traffic.
2006,
Pubmed Hales,
Identification and characterization of a family of Rab11-interacting proteins.
2001,
Pubmed Hickson,
Arfophilins are dual Arf/Rab 11 binding proteins that regulate recycling endosome distribution and are related to Drosophila nuclear fallout.
2003,
Pubmed Honda,
Targeting of Arf-1 to the early Golgi by membrin, an ER-Golgi SNARE.
2005,
Pubmed Inoue,
Arf GAPs and their interacting proteins.
2007,
Pubmed Inoue,
Arf GTPase-activating protein ASAP1 interacts with Rab11 effector FIP3 and regulates pericentrosomal localization of transferrin receptor-positive recycling endosome.
2008,
Pubmed Jenkins,
Ciliary targeting of olfactory CNG channels requires the CNGB1b subunit and the kinesin-2 motor protein, KIF17.
2006,
Pubmed Junutula,
Molecular characterization of Rab11 interactions with members of the family of Rab11-interacting proteins.
2004,
Pubmed Kahn,
Nomenclature for the human Arf family of GTP-binding proteins: ARF, ARL, and SAR proteins.
2006,
Pubmed Lee,
Bi-directional protein transport between the ER and Golgi.
2004,
Pubmed Leroux,
Taking vesicular transport to the cilium.
2007,
Pubmed Luo,
Kinetic analysis of GTP hydrolysis catalysed by the Arf1-GTP-ASAP1 complex.
2007,
Pubmed Luo,
Mutational analysis of the Arf1*GTP/Arf GAP interface reveals an Arf1 mutant that selectively affects the Arf GAP ASAP1.
2005,
Pubmed Markgraf,
Rab cascades and tethering factors in the endomembrane system.
2007,
Pubmed Meyers,
Formation of mutually exclusive Rab11 complexes with members of the family of Rab11-interacting proteins regulates Rab11 endocytic targeting and function.
2002,
Pubmed Moritz,
Mutant rab8 Impairs docking and fusion of rhodopsin-bearing post-Golgi membranes and causes cell death of transgenic Xenopus rods.
2001,
Pubmed
,
Xenbase Nachury,
A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis.
2007,
Pubmed Nie,
Arf GAPs and membrane traffic.
2006,
Pubmed Nie,
Arf and its many interactors.
2003,
Pubmed Nie,
A BAR domain in the N terminus of the Arf GAP ASAP1 affects membrane structure and trafficking of epidermal growth factor receptor.
2006,
Pubmed Novick,
Interactions between Rabs, tethers, SNAREs and their regulators in exocytosis.
2006,
Pubmed Omori,
Elipsa is an early determinant of ciliogenesis that links the IFT particle to membrane-associated small GTPase Rab8.
2008,
Pubmed Pasqualato,
The structural GDP/GTP cycle of Rab11 reveals a novel interface involved in the dynamics of recycling endosomes.
2004,
Pubmed Peter,
BAR domains as sensors of membrane curvature: the amphiphysin BAR structure.
2004,
Pubmed Prekeris,
A Rab11/Rip11 protein complex regulates apical membrane trafficking via recycling endosomes.
2000,
Pubmed Randazzo,
Arf GAPs: multifunctional proteins that regulate membrane traffic and actin remodelling.
2004,
Pubmed Rink,
Rab conversion as a mechanism of progression from early to late endosomes.
2005,
Pubmed Rogers,
The exocyst localizes to the primary cilium in MDCK cells.
2004,
Pubmed Roland,
Myosin Vb interacts with Rab8a on a tubular network containing EHD1 and EHD3.
2007,
Pubmed Rosenbaum,
Intraflagellar transport.
2002,
Pubmed Satoh,
Rab11 mediates post-Golgi trafficking of rhodopsin to the photosensitive apical membrane of Drosophila photoreceptors.
2005,
Pubmed Schonteich,
Molecular characterization of Rab11-FIP3 binding to ARF GTPases.
2007,
Pubmed Shiba,
Structural basis for Rab11-dependent membrane recruitment of a family of Rab11-interacting protein 3 (FIP3)/Arfophilin-1.
2006,
Pubmed Shin,
Identification of arfophilin, a target protein for GTP-bound class II ADP-ribosylation factors.
1999,
Pubmed Singla,
The primary cilium as the cell's antenna: signaling at a sensory organelle.
2006,
Pubmed Tam,
Mislocalized rhodopsin does not require activation to cause retinal degeneration and neurite outgrowth in Xenopus laevis.
2006,
Pubmed
,
Xenbase Tam,
Identification of an outer segment targeting signal in the COOH terminus of rhodopsin using transgenic Xenopus laevis.
2000,
Pubmed
,
Xenbase Urbé,
Rab11, a small GTPase associated with both constitutive and regulated secretory pathways in PC12 cells.
1993,
Pubmed Volpicelli-Daley,
Isoform-selective effects of the depletion of ADP-ribosylation factors 1-5 on membrane traffic.
2005,
Pubmed Wilson,
The FIP3-Rab11 protein complex regulates recycling endosome targeting to the cleavage furrow during late cytokinesis.
2005,
Pubmed Yoshimura,
Functional dissection of Rab GTPases involved in primary cilium formation.
2007,
Pubmed Zerial,
Rab proteins as membrane organizers.
2001,
Pubmed Zhang,
Sec15 is an effector for the Rab11 GTPase in mammalian cells.
2004,
Pubmed
