論文 - 詳細
| RRC ID | 59434 |
|---|---|
| 著者 | Alqadah A, Hsieh YW, Xiong R, Lesch BJ, Chang C, Chuang CF. |
| タイトル | A universal transportin protein drives stochastic choice of olfactory neurons via specific nuclear import of a sox-2-activating factor. |
| ジャーナル | Proc Natl Acad Sci U S A |
| Abstract |
Stochastic neuronal cell fate choice involving notch-independent mechanisms is a poorly understood biological process. The Caenorhabditis elegans AWC olfactory neuron pair asymmetrically differentiates into the default AWCOFF and induced AWCON subtypes in a stochastic manner. Stochastic choice of the AWCON subtype is established using gap junctions and SLO BK potassium channels to repress a calcium-activated protein kinase pathway. However, it is unknown how the potassium channel-repressed calcium signaling is translated into the induction of the AWCON subtype. Here, we identify a detailed working mechanism of how the homeodomain-like transcription factor NSY-7, previously described as a repressor in the maintenance of AWC asymmetry, couples SLO BK potassium channels to transactivation of sox-2 expression for the induction of the AWCON subtype through the identification of a unique imb-2 (transportin 1) allele. imb-2 loss-of-function mutants are not viable; however, we identify a viable imb-2 allele from an unbiased forward genetic screen that reveals a specific role of imb-2 in AWC olfactory neuron asymmetry. IMB-2 specifically drives nuclear import of NSY-7 within AWC neurons to transactivate the expression of the high mobility group (HMG)-box transcription factor SOX-2 for the specification of the AWCON subtype. This study provides mechanistic insight into how NSY-7 couples SLO BK potassium channels to transactivation of sox-2 expression for the induction of the AWCON subtype. Our findings also provide structure-function insight into a conserved amino acid residue of transportins in brain development and suggest its dysfunction may lead to human neurological disorders. |
| 巻・号 | 116(50) |
| ページ | 25137-25146 |
| 公開日 | 2019-12-10 |
| DOI | 10.1073/pnas.1908168116 |
| PII | 1908168116 |
| PMID | 31767767 |
| PMC | PMC6911211 |
| MeSH | Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Calcium Signaling / physiology Cell Nucleus / metabolism* Gap Junctions / metabolism Karyopherins / genetics Karyopherins / metabolism* Olfactory Receptor Neurons / metabolism* SOXB1 Transcription Factors / genetics SOXB1 Transcription Factors / metabolism* Stochastic Processes |
| IF | 9.58 |
| 引用数 | 0 |
| 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 | 2 |
| 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 | |
| 線虫 | tm1303 tm6328 tm6405 tm3036 tm1100 tm7139 |