| RRC ID |
11851
|
| 著者 |
Omori Y, Chaya T, Katoh K, Kajimura N, Sato S, Muraoka K, Ueno S, Koyasu T, Kondo M, Furukawa T.
|
| タイトル |
Negative regulation of ciliary length by ciliary male germ cell-associated kinase (Mak) is required for retinal photoreceptor survival.
|
| ジャーナル |
Proc Natl Acad Sci U S A
|
| Abstract |
Cilia function as cell sensors in many organs, and their disorders are referred to as "ciliopathies." Although ciliary components and transport machinery have been well studied, regulatory mechanisms of ciliary formation and maintenance are poorly understood. Here we show that male germ cell-associated kinase (Mak) regulates retinal photoreceptor ciliary length and subcompartmentalization. Mak was localized both in the connecting cilia and outer-segment axonemes of photoreceptor cells. In the Mak-null retina, photoreceptors exhibit elongated cilia and progressive degeneration. We observed accumulation of intraflagellar transport 88 (IFT88) and IFT57, expansion of kinesin family member 3A (Kif3a), and acetylated α-tubulin signals in the Mak-null photoreceptor cilia. We found abnormal rhodopsin accumulation in the Mak-null photoreceptor cell bodies at postnatal day 14. In addition, overexpression of retinitis pigmentosa 1 (RP1), a microtubule-associated protein localized in outer-segment axonemes, induced ciliary elongation, and Mak coexpression rescued excessive ciliary elongation by RP1. The RP1 N-terminal portion induces ciliary elongation and increased intensity of acetylated α-tubulin labeling in the cells and is phosphorylated by Mak. These results suggest that Mak is essential for the regulation of ciliary length and is required for the long-term survival of photoreceptors.
|
| 巻・号 |
107(52)
|
| ページ |
22671-6
|
| 公開日 |
2010-12-28
|
| DOI |
10.1073/pnas.1009437108
|
| PII |
1009437108
|
| PMID |
21148103
|
| PMC |
PMC3012466
|
| MeSH |
Amino Acid Sequence
Animals
Blotting, Western
Female
Gene Expression Regulation, Developmental
HEK293 Cells
Humans
In Situ Hybridization
Male
Mice
Mice, Knockout
Microscopy, Electron, Transmission
Microtubule-Associated Proteins / genetics
Microtubule-Associated Proteins / metabolism
Models, Biological
Molecular Sequence Data
NIH 3T3 Cells
Phosphorylation
Photoreceptor Connecting Cilium / metabolism*
Photoreceptor Connecting Cilium / ultrastructure
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism*
Retina / embryology
Retina / growth & development
Retina / metabolism*
Retinal Photoreceptor Cell Outer Segment / metabolism*
Retinal Photoreceptor Cell Outer Segment / ultrastructure
Reverse Transcriptase Polymerase Chain Reaction
Sequence Homology, Amino Acid
Time Factors
|
| IF |
9.412
|
| 引用数 |
70
|
|
WOS 分野
|
CELL BIOLOGY
|
| リソース情報 |
| 実験動物マウス |
RBRC00462 |
