June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Heterotrimeric kinesin-2 (KIF3) mediates transition zone and axoneme formation of mouse photoreceptors
Author Affiliations & Notes
  • Wolfgang Baehr
    Ophthalmology & Vis. Sci., University of Utah, Salt Lake City, UT
  • Yuxiao Wei
    Ophthalmology & Vis. Sci., University of Utah, Salt Lake City, UT
  • Cecinio Ronquillo
    Ophthalmology & Vis. Sci., University of Utah, Salt Lake City, UT
  • Robert E Marc
    Ophthalmology & Vis. Sci., University of Utah, Salt Lake City, UT
  • Jeanne M Frederick
    Ophthalmology & Vis. Sci., University of Utah, Salt Lake City, UT
  • Li Jiang
    Ophthalmology & Vis. Sci., University of Utah, Salt Lake City, UT
  • Footnotes
    Commercial Relationships Wolfgang Baehr, None; Yuxiao Wei, None; Cecinio Ronquillo, None; Robert Marc, None; Jeanne Frederick, None; Li Jiang, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 5522. doi:
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    • Get Citation

      Wolfgang Baehr, Yuxiao Wei, Cecinio Ronquillo, Robert E Marc, Jeanne M Frederick, Li Jiang; Heterotrimeric kinesin-2 (KIF3) mediates transition zone and axoneme formation of mouse photoreceptors. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5522.

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

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Abstract

Purpose: Anterograde intraflagellar transport (IFT) employing KIF3 motors has been implicated in outer segment protein trafficking. Here we examine the consequence of deletion of KIF3a, the obligatory subunit of KIF3, and IFT88, an IFT-B particle, during embryonic development and in the adult.

Methods: Embryonic conditional deletions of either KIF3A or IFT88 were generated by crossing Kif3afl/fl and Ift88fl/fl mice with Six3-Cre transgenic mice (prefix emb). KIF3A and IFT88 deletions in the adult mouse were achieved by mating with CreERT transgenic mice and inducing with tamoxifen-injection (prefix tam). Mutant phenotypes were analyzed by immunocytochemistry, electron microscopy and ERG.<br />

Results: In embKif3a-/- and in embIft88-/- mice, basal bodies failed to extend transition zones (connecting cilia) and form outer segments. Rhodopsin, cone pigments and other OS proteins accumulated in inner segments and photoreceptors degenerated. In tamKIF3a-/- and tamIFT88-/- adult mice, outer segments shortened and degenerated over 4-6 weeks. Fully mature tamKif3a-/- and tamIft88-/- photoreceptor axonemes failed to be maintained and disintegrated slowly. However, despite the absence of KIF3A or IFT88, rhodopsin and cone pigments trafficked normally for more than 2 weeks post-induction, a time interval over which the OS is completely renewed. The results demonstrate that IFT mediated by either KIF3 or IFT88 is not required for rhodopsin transport to the OS. Rather, anterograde IFT mediated by KIF3 participates in photoreceptor transition zone (PTZ) and axoneme formation.

Conclusions: KIF3 is essential for anterograde IFT and axoneme maintenance. Integral membrane proteins, rhodopsin and cone opsin, do not require KIF3- and IFT88-dependent IFT to traffic to photoreceptor outer segments.<br />

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