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Kif17 phosphorylation regulates photoreceptor outer segment turnover. BMC Cell Biol 2018 11 20;19(1):25

Date

11/22/2018

Pubmed ID

30458707

Pubmed Central ID

PMC6245759

DOI

10.1186/s12860-018-0177-9

Scopus ID

2-s2.0-85056802940   8 Citations

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.

Author List

Lewis TR, Kundinger SR, Link BA, Insinna C, Besharse JC

Author

Brian A. Link PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Animals
Animals, Genetically Modified
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Cell Line
Cilia
Humans
Kinesin
Mice, Inbred C57BL
Mutation
Phagosomes
Phosphorylation
Retinal Cone Photoreceptor Cells
Retinal Photoreceptor Cell Outer Segment
Zebrafish
Zebrafish Proteins
jenkins-FCD Prod-486 e3098984f26de787f5ecab75090d0a28e7f4f7c0