論文 - 詳細
| RRC ID | 75745 |
|---|---|
| 著者 | Wolman MA, Jain RA, Marsden KC, Bell H, Skinner J, Hayer KE, Hogenesch JB, Granato M. |
| タイトル | A genome-wide screen identifies PAPP-AA-mediated IGFR signaling as a novel regulator of habituation learning. |
| ジャーナル | Neuron |
| Abstract |
Habituation represents a fundamental form of learning, yet the underlying molecular genetic mechanisms are not well defined. Here we report on a genome-wide genetic screen, coupled with whole-genome sequencing, that identified 14 zebrafish startle habituation mutants including mutants of the vertebrate-specific gene pregnancy-associated plasma protein-aa (pappaa). PAPP-AA encodes an extracellular metalloprotease known to increase IGF bioavailability, thereby enhancing IGF receptor signaling. We find that pappaa is expressed by startle circuit neurons, and expression of wild-type but not a metalloprotease-inactive version of pappaa restores habituation in pappaa mutants. Furthermore, acutely inhibiting IGF1R function in wild-type reduces habituation, while activation of IGF1R downstream effectors in pappaa mutants restores habituation, demonstrating that pappaa promotes learning by acutely and locally increasing IGF bioavailability. In sum, our results define the first functional gene set for habituation learning in a vertebrate and identify PAPPAA-regulated IGF signaling as a novel mechanism regulating habituation learning. |
| 巻・号 | 85(6) |
| ページ | 1200-11 |
| 公開日 | 2015-3-18 |
| DOI | 10.1016/j.neuron.2015.02.025 |
| PII | S0896-6273(15)00140-3 |
| PMID | 25754827 |
| PMC | PMC4368495 |
| MeSH | Animals Behavior, Animal Female Genetic Testing / methods Genome, Archaeal* Learning / physiology* Mutation / genetics* Neurons / metabolism Pregnancy Pregnancy-Associated Plasma Protein-A / genetics Pregnancy-Associated Plasma Protein-A / metabolism* Receptor, IGF Type 1 / genetics Receptor, IGF Type 1 / metabolism* Signal Transduction / genetics* Zebrafish / metabolism* |
| IF | 14.415 |
| 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 | News |
| 各媒体での言及数の合計 | 16 |
| 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 | |
| ゼブラフィッシュ | hspGFFDMC130A |