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PMID: 21307337 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

IFT20 is required for opsin trafficking and photoreceptor outer segment development.

Molecular biology of the cell ·Vol. 22 ·No. 7 ·2011-04-00 ·Pages 921-30

Keady BT, Le YZ, Pazour GJ

Abstract

The light-detecting outer segments of vertebrate photoreceptors are cilia. Like other cilia, all materials needed for assembly and maintenance are synthesized in the cell body and transported into the cilium. The highly elaborated nature of the outer segment and its high rate of turnover necessitate unusually high levels of transport into the cilium. In this work, we examine the role of the IFT20 subunit of the intraflagellar transport (IFT) particle in photoreceptor cells. IFT20 was deleted in developing cones by a cone-specific Cre and in mature rods and cones by a tamoxifen-activatable Cre. Loss of IFT20 during cone development leads to opsin accumulation in the inner segment even when the connecting cilium and outer segment are still intact. With time this causes cone cell degeneration. Similarly, deletion of IFT20 in mature rods causes rapid accumulation of rhodopsin in the cell body, where it is concentrated at the Golgi complex. We further show that IFT20, acting both as part of the IFT particle and independent of the particle, binds to rhodopsin and RG-opsin. Since IFT20 dynamically moves between the Golgi complex and the connecting cilium, the current work suggests that rhodopsin and opsins are cargo for IFT transport.

MeSH Terms
Animals Carrier Proteins/genetics,metabolism Cilia/metabolism,ultrastructure Mice Mice, Knockout Opsins/metabolism Protein Transport Recombinant Fusion Proteins/genetics,metabolism Retinal Cone Photoreceptor Cells/cytology,physiology Retinal Photoreceptor Cell Outer Segment/physiology,ultrastructure Retinal Rod Photoreceptor Cells/cytology,physiology
Chemicals
Carrier Proteins Ift20 protein, mouse Opsins Recombinant Fusion Proteins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Keady Brian T
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Le Yun Zheng
Pazour Gregory J
References (40)
40 references, click to expand
  1. Targeted expression of Cre recombinase to cone photoreceptors in transgenic mice.
    Mol Vis. 2004 Dec 27;10:1011-8 PMID: 15635292
  2. Photoreceptor IFT complexes containing chaperones, guanylyl cyclase 1 and rhodopsin.
    Traffic. 2009 Jun;10(6):648-63 PMID: 19302411
  3. Chlamydomonas kinesin-II-dependent intraflagellar transport (IFT): IFT particles contain proteins required for ciliary assembly in Caenorhabditis elegans sensory neurons.
    J Cell Biol. 1998 May 18;141(4):993-1008 PMID: 9585417
  4. Intraflagellar transport.
    Nat Rev Mol Cell Biol. 2002 Nov;3(11):813-25 PMID: 12415299
  5. Development of the cone photoreceptor mosaic in the mouse retina revealed by fluorescent cones in transgenic mice.
    Mol Vis. 2003 Feb 15;9:31-42 PMID: 12592228
  6. A role for rhodopsin in a signal transduction cascade that regulates membrane trafficking and photoreceptor polarity.
    Vision Res. 2006 Dec;46(27):4427-33 PMID: 17010408
  7. Genetic evidence for selective transport of opsin and arrestin by kinesin-II in mammalian photoreceptors.
    Cell. 2000 Jul 21;102(2):175-87 PMID: 10943838
  8. The retinitis pigmentosa 1 protein is a photoreceptor microtubule-associated protein.
    J Neurosci. 2004 Jul 21;24(29):6427-36 PMID: 15269252
  9. The Golgin GMAP210/TRIP11 anchors IFT20 to the Golgi complex.
    PLoS Genet. 2008 Dec;4(12):e1000315 PMID: 19112494
  10. Intraflagellar transport genes are essential for differentiation and survival of vertebrate sensory neurons.
    Neuron. 2004 Jun 10;42(5):703-16 PMID: 15182712
  11. Cone opsin mislocalization in Rpe65-/- mice: a defect that can be corrected by 11-cis retinal.
    Invest Ophthalmol Vis Sci. 2005 Oct;46(10):3876-82 PMID: 16186377
  12. The Chlamydomonas reinhardtii BBSome is an IFT cargo required for export of specific signaling proteins from flagella.
    J Cell Biol. 2009 Dec 28;187(7):1117-32 PMID: 20038682
  13. Characterization of mouse IFT complex B.
    Cell Motil Cytoskeleton. 2009 Aug;66(8):457-68 PMID: 19253336
  14. A novel Usher protein network at the periciliary reloading point between molecular transport machineries in vertebrate photoreceptor cells.
    Hum Mol Genet. 2008 Jan 1;17(1):71-86 PMID: 17906286
  15. The intraflagellar transport protein IFT57 is required for cilia maintenance and regulates IFT-particle-kinesin-II dissociation in vertebrate photoreceptors.
    J Cell Sci. 2008 Jun 1;121(11):1907-15 PMID: 18492793
  16. Dysfunction of heterotrimeric kinesin-2 in rod photoreceptor cells and the role of opsin mislocalization in rapid cell death.
    Mol Biol Cell. 2010 Dec;21(23):4076-88 PMID: 20926680
  17. Deletion of IFT20 in the mouse kidney causes misorientation of the mitotic spindle and cystic kidney disease.
    J Cell Biol. 2008 Nov 3;183(3):377-84 PMID: 18981227
  18. Kinetics of rod outer segment renewal in the developing mouse retina.
    J Cell Biol. 1973 Sep;58(3):650-61 PMID: 4747920
  19. Intraflagellar transport and the sensory outer segment of vertebrate photoreceptors.
    Dev Dyn. 2008 Aug;237(8):1982-92 PMID: 18489002
  20. Synthesis, transport, and utilization of specific flagellar proteins during flagellar regeneration in Chlamydomonas.
    J Cell Biol. 1982 Jun;93(3):615-31 PMID: 7118994
  21. The renewal of photoreceptor cell outer segments.
    J Cell Biol. 1967 Apr;33(1):61-72 PMID: 6033942
  22. Intraflagellar transport motors in cilia: moving along the cell's antenna.
    J Cell Biol. 2008 Jan 14;180(1):23-9 PMID: 18180368
  23. Identification of a nonsense mutation in the rod photoreceptor cGMP phosphodiesterase beta-subunit gene of the rd mouse.
    Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8322-6 PMID: 1656438
  24. SARA-regulated vesicular targeting underlies formation of the light-sensing organelle in mammalian rods.
    Cell. 2007 Aug 10;130(3):535-47 PMID: 17693260
  25. IFT20 links kinesin II with a mammalian intraflagellar transport complex that is conserved in motile flagella and sensory cilia.
    J Biol Chem. 2003 Sep 5;278(36):34211-8 PMID: 12821668
  26. Rods and cones in the mouse retina. I. Structural analysis using light and electron microscopy.
    J Comp Neurol. 1979 Nov 15;188(2):245-62 PMID: 500858
  27. The intraflagellar transport protein IFT20 is associated with the Golgi complex and is required for cilia assembly.
    Mol Biol Cell. 2006 Sep;17(9):3781-92 PMID: 16775004
  28. Efficient recombination in diverse tissues by a tamoxifen-inducible form of Cre: a tool for temporally regulated gene activation/inactivation in the mouse.
    Dev Biol. 2002 Apr 15;244(2):305-18 PMID: 11944939
  29. The intraflagellar transport protein, IFT88, is essential for vertebrate photoreceptor assembly and maintenance.
    J Cell Biol. 2002 Apr 1;157(1):103-13 PMID: 11916979
  30. Elipsa is an early determinant of ciliogenesis that links the IFT particle to membrane-associated small GTPase Rab8.
    Nat Cell Biol. 2008 Apr;10(4):437-44 PMID: 18364699
  31. Trafficking of membrane proteins to cone but not rod outer segments is dependent on heterotrimeric kinesin-II.
    J Neurosci. 2009 Nov 11;29(45):14287-98 PMID: 19906976
  32. Rhodopsin's carboxy-terminal cytoplasmic tail acts as a membrane receptor for cytoplasmic dynein by binding to the dynein light chain Tctex-1.
    Cell. 1999 Jun 25;97(7):877-87 PMID: 10399916
  33. Spatial distribution of intraflagellar transport proteins in vertebrate photoreceptors.
    Vision Res. 2008 Feb;48(3):413-23 PMID: 17931679
  34. The homodimeric kinesin, Kif17, is essential for vertebrate photoreceptor sensory outer segment development.
    Dev Biol. 2008 Apr 1;316(1):160-70 PMID: 18304522
  35. Intraflagellar transport molecules in ciliary and nonciliary cells of the retina.
    J Cell Biol. 2010 Apr 5;189(1):171-86 PMID: 20368623
  36. Analysis of kinesin-2 function in photoreceptor cells using synchronous Cre-loxP knockout of Kif3a with RHO-Cre.
    Invest Ophthalmol Vis Sci. 2006 Nov;47(11):5039-46 PMID: 17065525
  37. Targeting proteins to the ciliary membrane.
    Curr Top Dev Biol. 2008;85:115-49 PMID: 19147004
  38. Cone outer segment morphogenesis: taper change and distal invaginations.
    J Cell Biol. 1987 Nov;105(5):2267-77 PMID: 3680382
  39. Crystal structure of rhodopsin: a template for cone visual pigments and other G protein-coupled receptors.
    Biochim Biophys Acta. 2002 Oct 11;1565(2):168-82 PMID: 12409193
  40. Modeling ciliopathies: Primary cilia in development and disease.
    Curr Top Dev Biol. 2008;84:249-310 PMID: 19186246
Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1939-4586
Published
2011-04-00
Epub
2011-00-09
Pages
921-30
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC3069017
Subset
IM
Grants
NIDDK NIH HHS · P30 DK032520 · United States
NIGMS NIH HHS · R01 GM060992 · United States
NIDDK NIH HHS · DK32520 · United States
NIGMS NIH HHS · GM060992 · United States
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