PUBLICATION
Kif17 phosphorylation regulates photoreceptor outer segment turnover
- Authors
- Lewis, T.R., Kundinger, S.R., Link, B.A., Insinna, C., Besharse, J.C.
- ID
- ZDB-PUB-181127-27
- Date
- 2018
- Source
- BMC Cell Biology 19: 25 (Journal)
- Registered Authors
- Besharse, Joseph C., Lewis, Tylor, Link, Brian
- Keywords
- Cilia, Disc shedding, Intraflagellar transport, Kinesin, Phagocytosis, Photoreceptor, Retina
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Animals, Genetically Modified
- Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism
- Cell Line
- Cilia/metabolism
- Humans
- Kinesins/chemistry
- Kinesins/metabolism*
- Mice, Inbred C57BL
- Mutation/genetics
- Phagosomes/metabolism
- Phagosomes/ultrastructure
- Phosphorylation
- Retinal Cone Photoreceptor Cells/metabolism
- Retinal Cone Photoreceptor Cells/ultrastructure
- Retinal Photoreceptor Cell Outer Segment/metabolism*
- Zebrafish/metabolism*
- Zebrafish Proteins/chemistry
- Zebrafish Proteins/metabolism*
- PubMed
- 30458707 Full text @ BMC Cell Biol.
Citation
Lewis, T.R., Kundinger, S.R., Link, B.A., Insinna, C., Besharse, J.C. (2018) Kif17 phosphorylation regulates photoreceptor outer segment turnover. BMC Cell Biology. 19:25.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping