title: Arl3 and RP2 mediated assembly and traffic of membrane associated cilia proteins.
abstract: The traffic of proteins to the outer segment of photoreceptors is a fundamentally important process, which when perturbed results in photoreceptor cell death. Recent reports have revealed a novel pathway for the traffic of lipid-modified proteins involving the small GTPase Arl3 and its effectors PDEδ and Unc119. The retinitis pigmentosa protein RP2 is a GTPase activating protein (GAP) for Arl3 and also appears to regulate the assembly and traffic of membrane associated protein complexes. We recently identified the Gβ subunit of transducin (Gβ1) as a novel RP2 interacting protein. Our data support a role for RP2 in facilitating membrane association and traffic of Gβ1, potentially prior to the formation of the obligate Gβ:Gγ heterodimer. Here, we review the recent evidence that suggests that RP2 co-operates with Arl3 and its effectors in protein complex assembly and membrane specification for lipid-modified proteins. This is exemplified by the co-ordination of cilia associated traffic for heterotrimeric G proteins and we propose a model for the role of Arl3 and RP2 in this process.
authors.affiliation: UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: Nele
authors.initials: N
authors.lastname: Schwarz
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Hardcastle
authors.forename: Michael E
authors.initials: ME
authors.lastname: Cheetham
mesh_terms: D020727:ADP-Ribosylation Factors / Q000502:physiology*; D000818:Animals; D005136:Eye Proteins / Q000502:physiology*; D019204:GTP-Binding Proteins; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology*; D055212:Photoreceptor Connecting Cilium / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D055214:Retinal Photoreceptor Cell Outer Segment / Q000378:metabolism*; D012174:Retinitis Pigmentosa / Q000378:metabolism; D015293:Transducin / Q000378:metabolism
chemical_list: D005136:Eye Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C072178:RP2 protein, human; D019204:GTP-Binding Proteins; D015293:Transducin; D020727:ADP-Ribosylation Factors; C490247:ARL3 protein, human