論文 - 詳細
| RRC ID | 33200 |
|---|---|
| 著者 | Chaya T, Omori Y, Kuwahara R, Furukawa T. |
| タイトル | ICK is essential for cell type-specific ciliogenesis and the regulation of ciliary transport. |
| ジャーナル | EMBO J |
| Abstract |
Cilia and flagella are formed and maintained by intraflagellar transport (IFT) and play important roles in sensing and moving across species. At the distal tip of the cilia/flagella, IFT complexes turn around to switch from anterograde to retrograde transport; however, the underlying regulatory mechanism is unclear. Here, we identified ICK localization at the tip of cilia as a regulator of ciliary transport. In ICK-deficient mice, we found ciliary defects in neuronal progenitor cells with Hedgehog signal defects. ICK-deficient cells formed cilia with mislocalized Hedgehog signaling components. Loss of ICK caused the accumulation of IFT-A, IFT-B, and BBSome components at the ciliary tips. In contrast, overexpression of ICK induced the strong accumulation of IFT-B, but not IFT-A or BBSome components at ciliary tips. In addition, ICK directly phosphorylated Kif3a, while inhibition of this Kif3a phosphorylation affected ciliary formation. Our results suggest that ICK is a Kif3a kinase and essential for proper ciliogenesis in development by regulating ciliary transport at the tip of cilia. |
| 巻・号 | 33(11) |
| ページ | 1227-42 |
| 公開日 | 2014-6-2 |
| DOI | 10.1002/embj.201488175 |
| PII | embj.201488175 |
| PMID | 24797473 |
| PMC | PMC4198026 |
| MeSH | Animals Biological Transport Brain / abnormalities Cilia / genetics Cilia / metabolism* Female Flagella / genetics Flagella / metabolism* Hedgehog Proteins / genetics Hedgehog Proteins / metabolism Kinesins / genetics Kinesins / metabolism* Lung / abnormalities Male Mice Mice, Inbred C57BL Mice, Knockout Microtubule-Associated Proteins / genetics Microtubule-Associated Proteins / metabolism* Mutation Neurons / cytology Organ Specificity Phenotype Phosphorylation Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism* Retina / cytology Signal Transduction Stem Cells / ultrastructure |
| IF | 9.889 |
| 引用数 | 41 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| リソース情報 | |
| 遺伝子材料 | pCAGGSII-mICK (RDB13108) pCAGGSII-hICK (RDB13109) pCAGGSII-mICK-K33R (RDB13110) pCAGGSII-hICK-R272Q (RDB13111) pCAGGSII-mIFT57 (RDB13112) pCAGGSII-mBBS8 (RDB13113) pCAGGSII-mKIF3A (RDB13114) pCAGGSII-mIFT88 (RDB13115) pCAGGSII-mIFT140 (RDB13116) pGEX-4T-1-mKIF3A (delta 1-454 aa) (RDB13117) pBAsi-mU6-shKIF3A‐1 (RDB13118) pBAsi-mU6-shKIF3A‐2 (RDB13119) pBAsi-mU6-shKIF3A‐3 (RDB13120) |