Ccrk-Mak/Ick signaling is a ciliary transport regulator essential for retinal photoreceptor survival

Chaya, Taro; Maeda, Yamato; Tsutsumi, Ryotaro et al.

Life science alliance, 2024, 7(11)

Number of Access:804（2025-08-19 01:12 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/98261

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Title
Ccrk-Mak/Ick signaling is a ciliary transport regulator essential for retinal photoreceptor survival
Creator
NRID
1000050747087 1000050747087
researchmap permalink
chaya chaya
Scopus Author ID
37094720600 37094720600
CreatorName
Chaya, Taro
NRID
1000051004618 1000051004618
researchmap permalink
yamato.maeda yamato.maeda
CreatorName
Maeda, Yamato
NRID
1000070965706 1000070965706
CreatorName
Tsutsumi, Ryotaro
CreatorName
Ando, Makoto
CreatorName
Ma, Yujie
NRID
1000040403175 1000040403175
ORCID
0000-0002-1546-6239 0000-0002-1546-6239
researchmap permalink
nkaji666 nkaji666
CreatorName
Kajimura, Naoko
NRID
1000010246647 1000010246647
CreatorName
Tanaka, Teruyuki
NRID
1000050260609 1000050260609
researchmap permalink
read0083689 read0083689
Scopus Author ID
7403160171 7403160171
ORCID
0000-0003-4171-220X 0000-0003-4171-220X
CreatorName
Furukawa, Takahisa
Description
Chaya T., Maeda Y., Tsutsumi R., et al. Ccrk-Mak/Ick signaling is a ciliary transport regulator essential for retinal photoreceptor survival. Life science alliance 7, (2024); https://doi.org/10.26508/lsa.202402880.
Abstract
Primary cilia are microtubule-based sensory organelles whose dysfunction causes ciliopathies in humans. The formation, function, and maintenance of primary cilia depend crucially on intraflagellar transport (IFT); however, the regulatory mechanisms of IFT at ciliary tips are poorly understood. Here, we identified that the ciliopathy kinase Mak is a ciliary tip-localized IFT regulator that cooperatively acts with the ciliopathy kinase Ick, an IFT regulator. Simultaneous disruption of Mak and Ick resulted in loss of photoreceptor ciliary axonemes and severe retinal degeneration. Gene delivery of Ick and pharmacological inhibition of FGF receptors, Ick negative regulators, ameliorated retinal degeneration in Mak-/- mice. We also identified that Ccrk kinase is an upstream activator of Mak and Ick in retinal photoreceptor cells. Furthermore, the overexpression of Mak, Ick, and Ccrk and pharmacological inhibition of FGF receptors suppressed ciliopathy-related phenotypes caused by cytoplasmic dynein inhibition in cultured cells. Collectively, our results show that the Ccrk-Mak/Ick axis is an IFT regulator essential for retinal photoreceptor maintenance and present activation of Ick as a potential therapeutic approach for retinitis pigmentosa caused by MAK mutations.
Publisher
Life Science Alliance
Source Title
Life science alliance
Volume (Issue)
7(11)
Date of Issued
2024-11-01
Language
English
Handle URL
https://hdl.handle.net/11094/98261
eISSN
25751077
Relation.isIdenticalTo
DOI (Publisher Version)
https://doi.org/10.26508/lsa.202402880
Access Rights
open access
CopyRight
This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version
Version of Record
Category
学術雑誌論文 Journal Article