Chapter 5

Rhodopsin Traffics to the Rod Outer Segment in the Absence of Homodimeric and Heterotrimeric Kinesin-2

Li Jiang, Jeanne M. Frederick and Wolfgang Baehr

Abstract

Homodimeric (KIF17) and heterotrimeric kinesin-2 (KIF3A, KIF3B and KAP) molecular motors are essential for anterograde intraflagellar transport (IFT) among invertebrates. Here we show that deletion of KIF3A in embryonic mouse retina interferes with IFT by preventing transition zone and axoneme formation. Absence of outer segments leads to severe mistrafficking of rhodopsin and rapid degeneration. By contrast, deletion of KIF3A in the adult mouse by tamoxifen-induction reveals normal rhodopsin transport to outer segments with failure of outer segment (OS) maintenance. Germline deletion of KIF17, a motor that cooperates with heterotrimeric kinesin-2 among invertebrates, affected neither OS structure nor photoreceptor morphology/ function thereby excluding an essential role of KIF17 in photoreceptor IFT. A KIF3A/KIF17 double knockout phenocopies a rod-specific KIF3A knockout. We conclude IFT is not required for rhodopsin transport to the OS but rather, anterograde IFT mediated by KIF3 participates in photoreceptor transition zone (PTZ) and axoneme formation.

Total Pages: 74-85 (12)

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