title: Three-dimensional architecture of the rod sensory cilium and its disruption in retinal neurodegeneration.
abstract: Defects in primary cilia lead to devastating disease because of their roles in sensation and developmental signaling but much is unknown about ciliary structure and mechanisms of their formation and maintenance. We used cryo-electron tomography to obtain 3D maps of the connecting cilium and adjacent cellular structures of a modified primary cilium, the rod outer segment, from wild-type and genetically defective mice. The results reveal the molecular architecture of the cilium and provide insights into protein functions. They suggest that the ciliary rootlet is involved in cellular transport and stabilizes the axoneme. A defect in the BBSome membrane coat caused defects in vesicle targeting near the base of the cilium. Loss of the proteins encoded by the Cngb1 gene disrupted links between the disk and plasma membranes. The structures of the outer segment membranes support a model for disk morphogenesis in which basal disks are enveloped by the plasma membrane.
authors.affiliation: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Jared C
authors.initials: JC
authors.lastname: Gilliam
authors.forename: Juan T
authors.initials: JT
authors.lastname: Chang
authors.forename: Ivette M
authors.initials: IM
authors.lastname: Sandoval
authors.forename: Youwen
authors.initials: Y
authors.lastname: Zhang
authors.forename: Tiansen
authors.initials: T
authors.lastname: Li
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Pittler
authors.forename: Wah
authors.initials: W
authors.lastname: Chiu
authors.forename: Theodore G
authors.initials: TG
authors.lastname: Wensel
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002923:Cilia / Q000737:chemistry / Q000648:ultrastructure*; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D012160:Retina / Q000737:chemistry / Q000378:metabolism; D012164:Retinal Diseases / Q000473:pathology*; D012374:Rod Cell Outer Segment / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D022161:Transport Vesicles / Q000378:metabolism
chemical_list: C506281:BBS4 protein, mouse; C529481:Cngb1 protein, mouse; C469436:Crocc protein, mouse; D054815:Cyclic Nucleotide-Gated Cation Channels; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins