April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Heterotrimeric Kinesin-2 is Required for Trafficking of Membrane Proteins to Cone, but Not Rod, Outer Segments
Author Affiliations & Notes
  • W. Baehr
    Ophthal & Vis Sci, Univ of Utah Sch of Med, Salt Lake City, Utah
  • C. B. Watt
    Ophthal & Vis Sci, Univ of Utah Sch of Med, Salt Lake City, Utah
  • D. S. Williams
    Jules Stein Eye Institute, UCLA, Los Angeles, California
  • Y. Z. Le
    Medicine and Cell Biology, Univ of Oklahoma, Oklahoma City, Oklahoma
  • S. Li
    Ophthal & Vis Sci, Univ of Utah Sch of Med, Salt Lake City, Utah
  • C.-K. Chen
    Biochemistry, Virginia Commonwealth University, Richmond, Virginia
  • J. M. Frederick
    Ophthal & Vis Sci, Univ of Utah Sch of Med, Salt Lake City, Utah
  • P. Avasthi
    Ophthal & Vis Sci, Univ of Utah Sch of Med, Salt Lake City, Utah
  • Footnotes
    Commercial Relationships  W. Baehr, None; C.B. Watt, None; D.S. Williams, None; Y.Z. Le, None; S. Li, None; C.-K. Chen, None; J.M. Frederick, None; P. Avasthi, None.
  • Footnotes
    Support  NIH grant EY08123, FFB C-UT01-0705-0300
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 4797. doi:
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    • Get Citation

      W. Baehr, C. B. Watt, D. S. Williams, Y. Z. Le, S. Li, C.-K. Chen, J. M. Frederick, P. Avasthi; Heterotrimeric Kinesin-2 is Required for Trafficking of Membrane Proteins to Cone, but Not Rod, Outer Segments. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4797.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Kinesin-2 is an anterograde molecular motor localized to the connecting cilium and axoneme of mammalian photoreceptors. The role of kinesin-2 in anterograde intraflagellar transport (IFT) was examined by photoreceptor-specific deletions of KIF3A, its obligatory motor subunit.

Methods: : Rod- and cone-specific deletions of KIF3A were generated by mating floxed Kif3a mice with iCre75 transgenic mice expressing Cre recombinase in rods, or with Hrgp-Cre mice expressing Cre in cones, respectively. Rod and cone knockout retinas were analyzed by RT-PCR, immunocytochemistry, immunoblotting, ERG and electron microscopy.

Results: : In P28 central cones lacking KIF3A, phototransduction proteins (cone pigments, T, PDE6, CNGA3, GRK1, ARR4, GC1, GCAP1, Prom1) did not traffic to the outer segments, resulting in complete absence of a photopic ERG and progressive cone degeneration. Connecting cilia and axoneme fine structure appeared comparable to littermate controls at P13, although mutant cone outer segments revealed various states of membrane disorganization. Rod photoreceptors lacking KIF3A degenerated rapidly following P14. However, phototransduction components including rhodopsin, T, PDE6, CNGA1, GRK1, R9AP and Prom1 trafficked normally to the outer segments during the entire course of degeneration. Peripherin/rds trafficked normally to KIF3A-deleted rod and cone outer segments. Further, we show that KIF3A deletion did not affect anterograde trafficking of synaptic proteins (bassoon, ribeye, PSD95, UNC119 and complexins III and IV) in mutant rods or cones.

Conclusions: : Our results demonstrate that kinesin II powers anterograde IFT in cone, but not rod, photoreceptors even though rods and cones share similar structures and closely related or identical phototransduction polypeptides. The identities of the anterograde IFT motor in rods, or of anterograde motors transporting membrane proteins to the synaptic terminals, are unknown.

Keywords: photoreceptors • transgenics/knock-outs • retinal degenerations: cell biology 
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