Ciliary targeting motif VxPx directs assembly of a trafficking module through Arf4
Autor: | Beatrice M. Tam, Rytis Prekeris, Lisa Astuto-Gribble, Orson L. Moritz, Eric Schonteich, Hiroki Inoue, Jana Mazelova, Paul A. Randazzo, Dusanka Deretic |
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Rok vydání: | 2009 |
Předmět: |
Rhodopsin
GTPase-activating protein Xenopus Amino Acid Motifs Molecular Sequence Data GTPase Protein Sorting Signals Xenopus Proteins Article General Biochemistry Genetics and Molecular Biology Animals Genetically Modified Animals Small GTPase Amino Acid Sequence Cilia Molecular Biology Ciliary membrane Adaptor Proteins Signal Transducing General Immunology and Microbiology biology ADP-Ribosylation Factors Effector Hydrolysis General Neuroscience Cilium GTPase-Activating Proteins Retinal Degeneration Intracellular Membranes Actin cytoskeleton I-kappa B Kinase Protein Structure Tertiary Cell biology Actin Cytoskeleton Protein Transport Organ Specificity rab GTP-Binding Proteins biology.protein Mutant Proteins Guanosine Triphosphate Protein Binding trans-Golgi Network |
Zdroj: | The EMBO Journal. 28:183-192 |
ISSN: | 1460-2075 0261-4189 |
Popis: | 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. |
Databáze: | OpenAIRE |
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