Kif17 phosphorylation regulates photoreceptor outer segment turnover
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Abstract
BACKGROUND: KIF17, a kinesin-2 motor that functions in intraflagellar transport, can regulate the onset of photoreceptor outer segment development. However, the function of KIF17 in a mature photoreceptor remains unclear. Additionally, the ciliary localization of KIF17 is regulated by a C-terminal consensus sequence (KRKK) that is immediately adjacent to a conserved residue (mouse S1029/zebrafish S815) previously shown to be phosphorylated by CaMKII. Yet, whether this phosphorylation can regulate the localization, and thus function, of KIF17 in ciliary photoreceptors remains unknown. RESULTS: Using transgenic expression in zebrafish photoreceptors, we show that phospho-mimetic KIF17 has enhanced localization along the cone outer segment. Importantly, expression of phospho-mimetic KIF17 is associated with greatly enhanced turnover of the photoreceptor outer segment through disc shedding in a cell-autonomous manner, while genetic mutants of kif17 in zebrafish and mice have diminished disc shedding. Lastly, cone expression of constitutively active tCaMKII leads to a kif17-dependent increase in disc shedding. CONCLUSIONS: Taken together, our data support a model in which phosphorylation of KIF17 promotes its photoreceptor outer segment localization and disc shedding, a process essential for photoreceptor maintenance and homeostasis. While disc shedding has been predominantly studied in the context of the mechanisms underlying phagocytosis of outer segments by the retinal pigment epithelium, this work implicates photoreceptor-derived signaling in the underlying mechanisms of disc shedding.
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More recent work has reported comparable phagosome numbers occurring at two peaks in the mouse and zebrafish RPE, with one peak after light onset and the other after lights-off.
“More recent work, however, has reported comparable phagosome numbers occurring at two peaks in the mouse and zebrafish RPE, with one peak after light onset and the other after lights-off (Lewis et al., 2018).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Lewis et al., 2018
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- Authors
- Lewis, T. R., Kundinger, S. R., Link, B. A., Insinna, C., & Besharse, J. C.
- Affiliations
- Medical College of Wisconsin (US)
- Corresponding author
- Lewis, Tylor R.
- Kundinger, Sean R.
- Link, Brian A.
- Insinna, Christine
- Besharse, Joseph C.
- Venue
- BMC Cell Biology
- Published
- 2018-11-20
- Volume
- 19
- Issue
- 1
- Pages
- 25-25
- ISSN
- 1471-2121 (ISSN-L)
- PMC
- PMC6245759
- OpenAlex
- W2900969187
- Cited by
- 35
- References
- 58
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 8 · 2022: 10 · 2021: 2 · 2020: 6 · 2019: 3
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Cell Biology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Eye Institute (R01 EY03222, R01 EY014167, T32 EY014537, P30 EY001931)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Keywords
- KIF17, CaMKII phosphorylation, ciliary photoreceptors, cone photoreceptors, intraflagellar transport, zebrafish, mice
- MeSH terms
- Amino Acid Sequence, Animals, Cell Line, Cilia, Humans, Mice, Inbred C57BL, Mutation, Phagosomes, Phosphorylation, Zebrafish, Kinesins, Retinal Cone Photoreceptor Cells, Zebrafish Proteins, Animals, Genetically Modified, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Retinal Photoreceptor Cell Outer Segment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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