Three-dimensional architecture of the rod sensory cilium and its disruption in retinal neurodegeneration

Jared C. Gilliam; Juan T. Chang; Ivette M. Sandoval; Youwen Zhang; Tiansen Li; Steven J. Pittler; Wah Chiu; Theodore G. Wensel

doi:10.1016/j.cell.2012.10.038

Three-dimensional architecture of the rod sensory cilium and its disruption in retinal neurodegeneration

Jared C. Gilliam, Juan T. Chang, Ivette M. Sandoval, Youwen Zhang, Tiansen Li, Steven J. Pittler, Wah Chiu, Theodore G. Wensel

Research output: Contribution to journal › Article › peer-review

120 Scopus citations

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. PaperFlick:

Original language	English (US)
Pages (from-to)	1029-1041
Number of pages	13
Journal	Cell
Volume	151
Issue number	5
DOIs	https://doi.org/10.1016/j.cell.2012.10.038
State	Published - Nov 21 2012

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.cell.2012.10.038

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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. PaperFlick:",

author = "Gilliam, {Jared C.} and Chang, {Juan T.} and Sandoval, {Ivette M.} and Youwen Zhang and Tiansen Li and Pittler, {Steven J.} and Wah Chiu and Wensel, {Theodore G.}",

note = "Funding Information: This work was supported in part by grants from the NIH (EY011900 and EY07981 to T.G.W., P41RR002250 to W.C., EY018143 to S.J.P., EY10309 and EY10581 to T.L., support for I.M.S. by EY011731, an NIH NRSA trainee appointment on grant T32EY007001 to J.C.G., and Vision Research Core Grant EY002520) and by the Robert Welch Foundation (Q-0035 to T.G.W. and Q1242 to W.C.). We thank Mr. Ralph Nichols for help with electron microscopy of fixed samples, Dr. Vera Moiseenkova-Bell for help in the early stages of the project, and Dr. Alecia Gross for helpful suggestions and pilot experiments. ",

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AU - Gilliam, Jared C.

AU - Chang, Juan T.

AU - Sandoval, Ivette M.

AU - Zhang, Youwen

AU - Li, Tiansen

AU - Pittler, Steven J.

AU - Chiu, Wah

AU - Wensel, Theodore G.

N1 - Funding Information: This work was supported in part by grants from the NIH (EY011900 and EY07981 to T.G.W., P41RR002250 to W.C., EY018143 to S.J.P., EY10309 and EY10581 to T.L., support for I.M.S. by EY011731, an NIH NRSA trainee appointment on grant T32EY007001 to J.C.G., and Vision Research Core Grant EY002520) and by the Robert Welch Foundation (Q-0035 to T.G.W. and Q1242 to W.C.). We thank Mr. Ralph Nichols for help with electron microscopy of fixed samples, Dr. Vera Moiseenkova-Bell for help in the early stages of the project, and Dr. Alecia Gross for helpful suggestions and pilot experiments.

PY - 2012/11/21

Y1 - 2012/11/21

N2 - 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. PaperFlick:

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Three-dimensional architecture of the rod sensory cilium and its disruption in retinal neurodegeneration

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