title: The retinitis pigmentosa protein RP2 links pericentriolar vesicle transport between the Golgi and the primary cilium.
abstract: Photoreceptors are complex ciliated sensory neurons. The basal body and periciliary ridge of photoreceptors function in association with the Golgi complex to regulate the export of proteins from the inner segment to the outer segment sensory axoneme. Here, we show that the retinitis pigmentosa protein RP2, which is a GTPase activating protein (GAP) for Arl3, localizes to the ciliary apparatus, namely the basal body and the associated centriole at the base of the photoreceptor cilium. Targeting to the ciliary base was dependent on N-terminal myristoylation. RP2 also localized to the Golgi and periciliary ridge of photoreceptors, which suggested a role for RP2 in regulating vesicle traffic and docking. To explore this hypothesis, we investigated the effect of RP2 depletion and the expression of a constitutively active form of Arl3 (Q71L) on pericentriolar vesicle transport. Kif3a, a component of intraflagellar transport (IFT), is important in cilia maintenance and transport of proteins through the connecting cilium in photoreceptors. Similar to Kif3a and Arl3 depletion, loss of RP2 led to fragmentation of the Golgi network. Depletion of RP2 and dysregulation of Arl3 resulted in dispersal of vesicles cycling cargo from the Golgi complex to the cilium, including the IFT protein IFT20. We propose that RP2 regulation of Arl3 is important for maintaining Golgi cohesion, facilitating the transport and docking of vesicles and thereby carrying proteins to the base of the photoreceptor connecting cilium for transport to the outer segment.
authors.affiliation: UCL Institute of Ophthalmology, London, UK.
authors.forename: R Jane
authors.initials: RJ
authors.lastname: Evans
authors.forename: Nele
authors.initials: N
authors.lastname: Schwarz
authors.forename: Kerstin
authors.initials: K
authors.lastname: Nagel-Wolfrum
authors.forename: Uwe
authors.initials: U
authors.lastname: Wolfrum
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 / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D002502:Centrioles / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism; D002924:Ciliary Body / Q000378:metabolism*; D005136:Eye Proteins / Q000502:physiology*; D019204:GTP-Binding Proteins; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D010786:Photoreceptor Cells / Q000378:metabolism*; D012174:Retinitis Pigmentosa / Q000378:metabolism*; D022161:Transport Vesicles / Q000378:metabolism
chemical_list: D005136:Eye Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C072178:RP2 protein, human; D019204:GTP-Binding Proteins; D020727:ADP-Ribosylation Factors; C490247:ARL3 protein, human