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J Biol Chem. 2015 May 15;290(20):12765-78. doi: 10.1074/jbc.M115.638437. Epub 2015 Mar 30.

Heterotrimeric kinesin-2 (KIF3) mediates transition zone and axoneme formation of mouse photoreceptors.

Author information

1
From the Departments of Ophthalmology and Visual Sciences and li.jiang@hsc.utah.edu.
2
From the Departments of Ophthalmology and Visual Sciences and.
3
the Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294, and.
4
From the Departments of Ophthalmology and Visual Sciences and the Department of Biology, University of Utah, Salt Lake City, Utah 84112 Neurobiology and Anatomy, University of Utah Health Science Center, Salt Lake City, Utah 84132, wbaehr@hsc.utah.edu.

Abstract

Anterograde intraflagellar transport (IFT) employing kinesin-2 molecular motors has been implicated in trafficking of photoreceptor outer segment proteins. We generated embryonic retina-specific (prefix "emb") and adult tamoxifen-induced (prefix "tam") deletions of KIF3a and IFT88 in adult mice to study photoreceptor ciliogenesis and protein trafficking. In (emb)Kif3a(-/-) and in (emb)Ift88(-/-) mice, basal bodies failed to extend transition zones (connecting cilia) with outer segments, and visual pigments mistrafficked. In contrast, (tam)Kif3a(-/-) and (tam)Ift88(-/-) photoreceptor axonemes disintegrated slowly post-induction, starting distally, but rhodopsin and cone pigments trafficked normally for more than 2 weeks, a time interval during which the outer segment is completely renewed. The results demonstrate that visual pigments transport to the retinal outer segment despite removal of KIF3 and IFT88, and KIF3-mediated anterograde IFT is responsible for photoreceptor transition zone and axoneme formation.

KEYWORDS:

IFT88; KIF3A; anterograde intraflagellar transport (IFT); cilia; conditional IFT88 knockout; conditional KIF3A knockout; gene knockout; heterotrimeric kinesin-2; homologous recombination; intraflagellar transport; photoreceptor; retinal degeneration

PMID:
25825494
PMCID:
PMC4432293
DOI:
10.1074/jbc.M115.638437
[Indexed for MEDLINE]
Free PMC Article

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