Home LiteratureArticle Details
PMID: 19906976 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Trafficking of membrane proteins to cone but not rod outer segments is dependent on heterotrimeric kinesin-II.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 29 ·No. 45 ·2009-11-11 ·Pages 14287-98

Avasthi P, Watt CB, Williams DS, Le YZ, Li S, Chen CK, Marc RE, Frederick JM, Baehr W

Abstract

Heterotrimeric kinesin-II is a molecular motor localized to the inner segment, connecting cilium and axoneme of mammalian photoreceptors. Our purpose was to identify the role of kinesin-II in anterograde intraflagellar transport by photoreceptor-specific deletions of kinesin family member 3A (KIF3A), its obligatory motor subunit. In cones lacking KIF3A, membrane proteins involved in phototransduction did not traffic to the outer segments resulting in complete absence of a photopic electroretinogram and progressive cone degeneration. Rod photoreceptors lacking KIF3A degenerated rapidly between 2 and 4 weeks postnatally, but the phototransduction components including rhodopsin trafficked to the outer segments during the course of degeneration. Furthermore, KIF3A deletion did not affect synaptic anterograde trafficking. The results indicate that trafficking of membrane proteins to the outer segment is dependent on kinesin-II in cone, but not rod photoreceptors, even though rods and cones share similar structures, and closely related phototransduction polypeptides.

MeSH Terms
Animals Kinesins/genetics,metabolism Membrane Proteins/metabolism Mice Mice, Knockout Mice, Transgenic Microtubule-Associated Proteins/metabolism Protein Transport/physiology Retina/growth & development,physiopathology,ultrastructure Retinal Cone Photoreceptor Cells/physiology,ultrastructure Retinal Degeneration/physiopathology Retinal Pigments/metabolism Retinal Rod Photoreceptor Cells/physiology Rhodopsin/metabolism Synapses/physiology Time Factors
Chemicals
Kif3a protein, mouse Membrane Proteins Microtubule-Associated Proteins Retinal Pigments Rhodopsin Kinesins
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Avasthi Prachee
Department of Ophthalmology, University of Utah Health Science Center, Salt Lake City, Utah 84132, USA.
Watt Carl B
Williams David S
Le Yun Z
Li Sha
Chen Ching-Kang
Marc Robert E
Frederick Jeanne M
Baehr Wolfgang
References (74)
74 references, click to expand
  1. Impaired photoreceptor protein transport and synaptic transmission in a mouse model of Bardet-Biedl syndrome.
    Vision Res. 2007 Dec;47(27):3394-407 PMID: 18022666
  2. Downregulation of cone-specific gene expression and degeneration of cone photoreceptors in the Rpe65-/- mouse at early ages.
    Invest Ophthalmol Vis Sci. 2005 Apr;46(4):1473-9 PMID: 15790918
  3. Fifty years later: the disk goes to the prom.
    J Clin Invest. 2008 Aug;118(8):2681-4 PMID: 18654671
  4. Mouse opsin promoter-directed Cre recombinase expression in transgenic mice.
    Mol Vis. 2006 Apr 18;12:389-98 PMID: 16636658
  5. Kinesin-II is preferentially targeted to assembling cilia and is required for ciliogenesis and normal cytokinesis in Tetrahymena.
    Mol Biol Cell. 1999 Oct;10(10):3081-96 PMID: 10512852
  6. Organization of vesicular trafficking in epithelia.
    Nat Rev Mol Cell Biol. 2005 Mar;6(3):233-47 PMID: 15738988
  7. Characterization of peripherin/rds and rom-1 transport in rod photoreceptors of transgenic and knockout animals.
    Invest Ophthalmol Vis Sci. 2006 May;47(5):2150-60 PMID: 16639027
  8. Targeted expression of Cre recombinase to cone photoreceptors in transgenic mice.
    Mol Vis. 2004 Dec 27;10:1011-8 PMID: 15635292
  9. Rod outer segment disk shedding in rat retina: relationship to cyclic lighting.
    Science. 1976 Dec 3;194(4269):1071-4 PMID: 982063
  10. Impaired opsin targeting and cone photoreceptor migration in the retina of mice lacking the cyclic nucleotide-gated channel CNGA3.
    Invest Ophthalmol Vis Sci. 2005 Apr;46(4):1516-24 PMID: 15790924
  11. Complement factor H deficiency in aged mice causes retinal abnormalities and visual dysfunction.
    Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16651-6 PMID: 17921253
  12. Transport to the photoreceptor outer segment by myosin VIIa and kinesin II.
    Vision Res. 2002 Feb;42(4):455-62 PMID: 11853761
  13. The kinesin motor KIF3A is a component of the presynaptic ribbon in vertebrate photoreceptors.
    J Neurosci. 1999 Feb 1;19(3):1027-37 PMID: 9920666
  14. Nuclear targeting determinants of the phage P1 cre DNA recombinase.
    Nucleic Acids Res. 1999 Dec 15;27(24):4703-9 PMID: 10572169
  15. The renewal of photoreceptor cell outer segments.
    J Cell Biol. 1967 Apr;33(1):61-72 PMID: 6033942
  16. Mutant prominin 1 found in patients with macular degeneration disrupts photoreceptor disk morphogenesis in mice.
    J Clin Invest. 2008 Aug;118(8):2908-16 PMID: 18654668
  17. Photoreceptor localization of the KIF3A and KIF3B subunits of the heterotrimeric microtubule motor kinesin II in vertebrate retina.
    Exp Eye Res. 1999 Nov;69(5):491-503 PMID: 10548469
  18. 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
  19. Role of xklp3, a subunit of the Xenopus kinesin II heterotrimeric complex, in membrane transport between the endoplasmic reticulum and the Golgi apparatus.
    J Cell Biol. 1998 Dec 14;143(6):1559-73 PMID: 9852151
  20. Cyclic nucleotide-gated ion channels.
    Physiol Rev. 2002 Jul;82(3):769-824 PMID: 12087135
  21. Intraflagellar transport.
    Nat Rev Mol Cell Biol. 2002 Nov;3(11):813-25 PMID: 12415299
  22. KIF3A/B: a heterodimeric kinesin superfamily protein that works as a microtubule plus end-directed motor for membrane organelle transport.
    J Cell Biol. 1995 Sep;130(6):1387-99 PMID: 7559760
  23. Intraflagellar transport motors in cilia: moving along the cell's antenna.
    J Cell Biol. 2008 Jan 14;180(1):23-9 PMID: 18180368
  24. Post-Golgi trafficking of rhodopsin in retinal photoreceptors.
    Eye (Lond). 1998;12 ( Pt 3b):526-30 PMID: 9775213
  25. Different roles for KIF17 and kinesin II in photoreceptor development and maintenance.
    Dev Dyn. 2009 Sep;238(9):2211-22 PMID: 19384852
  26. Disruption of kinesin II function using a dominant negative-acting transgene in Xenopus laevis rods results in photoreceptor degeneration.
    Invest Ophthalmol Vis Sci. 2003 Aug;44(8):3614-21 PMID: 12882815
  27. Ciliary targeting of olfactory CNG channels requires the CNGB1b subunit and the kinesin-2 motor protein, KIF17.
    Curr Biol. 2006 Jun 20;16(12):1211-6 PMID: 16782012
  28. Characterization of rhodopsin mis-sorting and constitutive activation in a transgenic rat model of retinitis pigmentosa.
    Invest Ophthalmol Vis Sci. 2000 May;41(6):1546-53 PMID: 10798675
  29. 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
  30. The primordial, blue-cone color system of the mouse retina.
    J Neurosci. 2005 Jun 1;25(22):5438-45 PMID: 15930394
  31. 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
  32. Isolation of a sea urchin egg kinesin-related protein using peptide antibodies.
    J Cell Sci. 1992 Feb;101 ( Pt 2):291-301 PMID: 1629246
  33. Focus on molecules: prominin-1 (CD133).
    Exp Eye Res. 2007 Nov;85(5):585-6 PMID: 16733052
  34. Membrane trafficking of heterotrimeric G proteins via the endoplasmic reticulum and Golgi.
    Mol Biol Cell. 2002 Sep;13(9):3294-302 PMID: 12221133
  35. 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
  36. A model for transport of membrane-associated phototransduction polypeptides in rod and cone photoreceptor inner segments.
    Vision Res. 2008 Feb;48(3):442-52 PMID: 17949773
  37. Mpp4 is required for proper localization of plasma membrane calcium ATPases and maintenance of calcium homeostasis at the rod photoreceptor synaptic terminals.
    Hum Mol Genet. 2007 May 1;16(9):1017-29 PMID: 17341488
  38. Structurally and functionally unique complexins at retinal ribbon synapses.
    J Cell Biol. 2005 May 23;169(4):669-80 PMID: 15911881
  39. R9AP, a membrane anchor for the photoreceptor GTPase accelerating protein, RGS9-1.
    Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9755-60 PMID: 12119397
  40. Secretory protein trafficking and organelle dynamics in living cells.
    Annu Rev Cell Dev Biol. 2000;16:557-89 PMID: 11031247
  41. Bbs2-null mice have neurosensory deficits, a defect in social dominance, and retinopathy associated with mislocalization of rhodopsin.
    Proc Natl Acad Sci U S A. 2004 Nov 23;101(47):16588-93 PMID: 15539463
  42. Rhodopsin-iCre transgenic mouse line for Cre-mediated rod-specific gene targeting.
    Genesis. 2005 Feb;41(2):73-80 PMID: 15682388
  43. Photoreceptor synaptic protein HRG4 (UNC119) interacts with ARL2 via a putative conserved domain.
    FEBS Lett. 2003 Jan 16;534(1-3):26-32 PMID: 12527357
  44. Bassoon, a novel zinc-finger CAG/glutamine-repeat protein selectively localized at the active zone of presynaptic nerve terminals.
    J Cell Biol. 1998 Jul 27;142(2):499-509 PMID: 9679147
  45. The murine cone photoreceptor: a single cone type expresses both S and M opsins with retinal spatial patterning.
    Neuron. 2000 Sep;27(3):513-23 PMID: 11055434
  46. Synaptic transmission at retinal ribbon synapses.
    Prog Retin Eye Res. 2005 Nov;24(6):682-720 PMID: 16027025
  47. Cloning and characterization of KAP3: a novel kinesin superfamily-associated protein of KIF3A/3B.
    Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8443-8 PMID: 8710890
  48. Retinal remodeling triggered by photoreceptor degenerations.
    J Comp Neurol. 2003 Sep 8;464(1):1-16 PMID: 12866125
  49. Membrane association of presynaptic cytomatrix protein bassoon.
    Biochem Biophys Res Commun. 2000 Aug 18;275(1):43-6 PMID: 10944438
  50. Situs inversus and embryonic ciliary morphogenesis defects in mouse mutants lacking the KIF3A subunit of kinesin-II.
    Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5043-8 PMID: 10220415
  51. 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
  52. Exclusive expression of C. elegans osm-3 kinesin gene in chemosensory neurons open to the external environment.
    J Mol Biol. 1995 Mar 31;247(3):377-89 PMID: 7714894
  53. Endomembrane trafficking of ras: the CAAX motif targets proteins to the ER and Golgi.
    Cell. 1999 Jul 9;98(1):69-80 PMID: 10412982
  54. Interaction and colocalization of CaBP4 and Unc119 (MRG4) in photoreceptors.
    Invest Ophthalmol Vis Sci. 2008 Jun;49(6):2366-75 PMID: 18296658
  55. Participation of the retinal pigment epithelium in the rod outer segment renewal process.
    J Cell Biol. 1969 Aug;42(2):392-403 PMID: 5792328
  56. Two anterograde intraflagellar transport motors cooperate to build sensory cilia on C. elegans neurons.
    Nat Cell Biol. 2004 Nov;6(11):1109-13 PMID: 15489852
  57. Kidney-specific inactivation of the KIF3A subunit of kinesin-II inhibits renal ciliogenesis and produces polycystic kidney disease.
    Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5286-91 PMID: 12672950
  58. The function of guanylate cyclase 1 and guanylate cyclase 2 in rod and cone photoreceptors.
    J Biol Chem. 2007 Mar 23;282(12):8837-47 PMID: 17255100
  59. Molecular dissection of the photoreceptor ribbon synapse: physical interaction of Bassoon and RIBEYE is essential for the assembly of the ribbon complex.
    J Cell Biol. 2005 Feb 28;168(5):825-36 PMID: 15728193
  60. 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
  61. Deletion of PrBP/delta impedes transport of GRK1 and PDE6 catalytic subunits to photoreceptor outer segments.
    Proc Natl Acad Sci U S A. 2007 May 22;104(21):8857-62 PMID: 17496142
  62. Evolution of the vertebrate eye: opsins, photoreceptors, retina and eye cup.
    Nat Rev Neurosci. 2007 Dec;8(12):960-76 PMID: 18026166
  63. Heterotrimeric kinesin-II is required for the assembly of motile 9+2 ciliary axonemes on sea urchin embryos.
    J Cell Biol. 1997 Sep 8;138(5):1009-22 PMID: 9281580
  64. 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
  65. The homodimeric kinesin, Kif17, is essential for vertebrate photoreceptor sensory outer segment development.
    Dev Biol. 2008 Apr 1;316(1):160-70 PMID: 18304522
  66. RIBEYE, a component of synaptic ribbons: a protein's journey through evolution provides insight into synaptic ribbon function.
    Neuron. 2000 Dec;28(3):857-72 PMID: 11163272
  67. Rpe65-/- and Lrat-/- mice: comparable models of leber congenital amaurosis.
    Invest Ophthalmol Vis Sci. 2008 Jun;49(6):2384-9 PMID: 18296659
  68. The retinal pigment epithelium in visual function.
    Physiol Rev. 2005 Jul;85(3):845-81 PMID: 15987797
  69. Trafficking of membrane-associated proteins to cone photoreceptor outer segments requires the chromophore 11-cis-retinal.
    J Neurosci. 2008 Apr 9;28(15):4008-14 PMID: 18400900
  70. Mammalian cones: disc shedding, phagocytosis, and renewal.
    Invest Ophthalmol Vis Sci. 1978 Feb;17(2):117-33 PMID: 415019
  71. Rhodopsin trafficking and its role in retinal dystrophies.
    Int Rev Cytol. 2000;195:215-67 PMID: 10603577
  72. Three-dimensional architecture of murine rod outer segments determined by cryoelectron tomography.
    J Cell Biol. 2007 Jun 4;177(5):917-25 PMID: 17535966
  73. Heterotrimeric kinesin II is the microtubule motor protein responsible for pigment dispersion in Xenopus melanophores.
    J Cell Biol. 1998 Dec 14;143(6):1547-58 PMID: 9852150
  74. Turnover of mouse photoreceptor outer segments in constant light and darkness.
    Invest Ophthalmol Vis Sci. 1979 Oct;18(10):1019-24 PMID: 478775
Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.3976-09.2009
Published
2009-11-11
Pages
14287-98
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC2788486
Subset
IM
Grants
NEI NIH HHS · R01 EY019298 · United States
NEI NIH HHS · EY013811 · United States
NEI NIH HHS · R56 EY013811 · United States
NEI NIH HHS · R01 EY007042 · United States
NEI NIH HHS · R01 EY019298-01 · United States
NEI NIH HHS · P30 EY014800-059003 · United States
NEI NIH HHS · EY014800-039003 · United States
NEI NIH HHS · EY13408 · United States
NEI NIH HHS · EY019298 · United States
NEI NIH HHS · R01 EY008123 · United States
NEI NIH HHS · R01 EY013408 · United States
NEI NIH HHS · R01 EY013811 · United States
NEI NIH HHS · R01 EY008123-21 · United States
NEI NIH HHS · EY08123 · United States
NEI NIH HHS · P30 EY014800 · United States
NEI NIH HHS · EY07042 · United States
External Links
PubMed source DOI: 10.1523/JNEUROSCI.3976-09.2009 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2