6533b7cefe1ef96bd1257c06
RESEARCH PRODUCT
PCARE and WASF3 regulate ciliary F-actin assembly that is required for the initiation of photoreceptor outer segment disk formation
Max D Van EssenRossano ButcherMarius UeffingAdem YildirimRob W.j. CollinQin LiuLonneke DuijkersKrzysztof PalczewskiAnita D M. HoogendoornNikoleta ArgyrouSylvia E. C. Van BeersumAlejandro GarantoUwe WolfrumJulio C. Corral-serranoKarsten BoldtRonald RoepmanRenate A A RuigrokIdeke J.c. LamersStef J.f. LetteboerJeroen Van ReeuwijkSanae SakamiMichael E. Cheethamsubject
ciliummacromolecular substancesSensory disorders Donders Center for Medical Neuroscience [Radboudumc 12]Actin-Related Protein 2-3 Complexchemistry.chemical_compoundMiceAll institutes and research themes of the Radboud University Medical Centerretinitis pigmentosaRetinitis pigmentosamedicineGeneticsAnimalsHumansCiliaRNA Small InterferingCiliary tipEye ProteinsCiliary membraneActinMice KnockoutMultidisciplinaryCiliumouter segmentsRetinalBiological Sciencesmedicine.diseaseRod Cell Outer SegmentPhotoreceptor outer segmentphotoreceptorActinsCell biologyWiskott-Aldrich Syndrome Protein FamilyDisease Models AnimalRenal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11]chemistryPNAS PlusGene Expression RegulationRetinal Cone Photoreceptor Cellssense organsactinCone-Rod DystrophiesVisual phototransductiondescription
Significance The photoreceptor outer segments are primary cilia, modified for phototransduction by incorporation of stacked opsin-loaded membrane disks that are continuously regenerated. This process is disrupted in several types of inherited retinal dystrophy, but the driving force remained unclear. We show that C2orf71/PCARE (photoreceptor cilium actin regulator), associated with inherited retinal dystrophy subtype RP54, efficiently recruits the Arp2/3 complex activator WASF3 to the cilium. This activates an actin dynamics-driven expansion of the ciliary tip, resembling membrane evagination in lamellipodia formation. Colocalization of this actin dynamics module to the base of the outer segments, and absence thereof in Pcare−/− mice, suggests PCARE-regulated actin dynamics as a critical process in outer segment disk formation.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2020-01-01 | Proceedings of the National Academy of Sciences USA |