論文 - 詳細
| RRC ID | 50576 |
|---|---|
| 著者 | Kobayashi D, Asano-Hoshino A, Nakakura T, Nishimaki T, Ansai S, Kinoshita M, Ogawa M, Hagiwara H, Yokoyama T. |
| タイトル | Loss of zinc finger MYND-type containing 10 (zmynd10) affects cilia integrity and axonemal localization of dynein arms, resulting in ciliary dysmotility, polycystic kidney and scoliosis in medaka (Oryzias latipes). |
| ジャーナル | Dev Biol |
| Abstract |
Cilia and flagella are hair-like organelles that project from the cell surface and play important roles in motility and sensory perception. Motility defects in cilia and flagella lead to primary ciliary dyskinesia (PCD), a rare human disease. Recently zinc finger MYND-type containing 10 (ZMYND10) was identified in humans as a PCD-associated gene. In this study, we use medaka fish as a model to characterize the precise functions of zmynd10. In medaka, zmynd10 is exclusively expressed in cells with motile cilia. Embryos with zmynd10 Morpholino knockdown exhibited a left-right (LR) defect associated with loss of motility in Kupffer's vesicle (KV) cilia. This immotility was caused by loss of the outer dynein arms, which is a characteristic ultrastructural phenotype in PCD. In addition, KV cilia in zmynd10 knockdown embryos had a swollen and wavy morphology. Together, these results suggest that zmynd10 is a multi-functional protein that has independent roles in axonemal localization of dynein arms and in formation and/or maintenance of cilia. The C-terminal region of zmynd10 has a MYND-type zinc finger domain (zf-MYND) that is important for its function. Our rescue experiment showed that the zmynd10-ΔC truncated protein, which lacks zf-MYND, was still partially functional, suggesting that zmynd10 has another functional domain besides zf-MYND. To analyze the later stages of development, we generated a zmynd10 knockout mutant using transcription activator-like effector nuclease (TALEN) technology. Adult mutants exhibited sperm dysmotility, scoliosis and progressive polycystic kidney. |
| 巻・号 | 430(1) |
| ページ | 69-79 |
| 公開日 | 2017-10-1 |
| DOI | 10.1016/j.ydbio.2017.08.016 |
| PII | S0012-1606(17)30202-6 |
| PMID | 28823919 |
| MeSH | Amino Acid Sequence Animals Axoneme / drug effects Axoneme / metabolism* Base Sequence Body Patterning / drug effects Body Patterning / genetics Cilia / drug effects Cilia / metabolism* Dyneins / metabolism* Embryo, Nonmammalian / drug effects Embryo, Nonmammalian / metabolism Epistasis, Genetic / drug effects Gene Expression Regulation, Developmental / drug effects Male Morpholinos / pharmacology Movement Oryzias / embryology Oryzias / genetics Oryzias / metabolism* Phenotype Polycystic Kidney Diseases / metabolism* Polycystic Kidney Diseases / pathology RNA, Messenger / genetics RNA, Messenger / metabolism Scoliosis / metabolism* Scoliosis / pathology Spermatozoa / metabolism Tumor Suppressor Proteins / chemistry Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism Zinc Fingers |
| IF | 2.896 |
| 引用数 | 6 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| メダカ | Hatching enzyme d-rR/TOKYO (MT837) zmynd10 (MT1419) |