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Li Jiang, Beatrice M Tam, Guoxin Ying, Jeanne M Frederick, William W Hauswirth, Orson L Moritz, Wolfgang Baehr; Photoreceptor KIF17 (Osm-3): a vestigial kinesin-2 motor. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1324. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Heterodimeric (KIF17, osm-3) participates in intraflagellar transport (IFT) building the distal segment of the chemosensory cilia in C. elegans. In this study, we attempted to identify the function of KIF17 in the photoreceptor sensory cilium, the outer segment (OS).
Full-length (FL) and motorless (ML) mutant kinesin-II (KIF17 and KIF3A) proteins were N-terminally tagged with EGFP or mCherry. Tagged proteins were expressed in mouse (AAV5), Xenopus laevis photoreceptors (as transgene), and in ciliated IMCD3 and NIH3T3 cells. In germline Kif17 knockout mice exon 4 of the Kif17 gene was deleted. Mutant phenotypes were analyzed by immunocytochemistry, western blotting, and/or ERG.
We show that tagged full-length mouse KIF17 trafficked to the OS and lined up along the mouse and Xenopus OS axoneme, while tagged KIF3A is present diffusely in the mouse and Xenopus inner segments. Tagged motorless KIF17-ML1(ΔAA 2-320) trafficked to OSs as cargo and caused photoreceptor degeneration. In contrast, KIF17-ML2(ΔAA 2-770) mutant lacking motor and neck domains was translocated to photoreceptor nuclei. When transiently expressed in ciliated IMCD3 or NIH3T3 cells, KIF17 located prominently to the tip of cilia, KIF17-ML1 to the nucleus and ciliary tip, while KIF17-ML2 accumulated in the nucleus. Co-expression of differentially tagged motorless mutants with KIF3A and KIF17 motors demonstrates that KIF3 is the IFT motor carrying motorless mutant KIF17-ML1 as cargo. Germline deletion of KIF17 affected neither OS structure nor photoreceptor function for up to two years. The phenotype of a rod-specific Kif3a knockout on a Kif17-/- background is identical to the Kif3a single knockout.
Expression of motorless KIF17 protein causes photoreceptor degeneration via dominant-negative interference with KIF3-dependent IFT. However, KIF17 is dispensable for photoreceptor morphology and function. A possible reason that KIF17 is not essential for photoreceptors as the continuous turnover of photoreceptor outer segments, where the distal tips of outer segments are removed by phagocytosis, eliminating the need for maintenance by KIF17.
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