A Genome-wide Screen Identifies PAPP-AA-Mediated IGFR Signaling as a Novel Regulator of Habituation Learning
| Autor: | Michael Granato, Hannah S. Bell, Roshan A. Jain, John B. Hogenesch, Julianne Skinner, Marc A. Wolman, Kurt C. Marsden, Katharina E. Hayer |
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| Rok vydání: | 2015 |
| Předmět: |
Neuroscience(all)
Mutant Regulator Biology Receptor IGF Type 1 03 medical and health sciences 0302 clinical medicine Genome Archaeal Pregnancy Animals Learning Pregnancy-Associated Plasma Protein-A Genetic Testing Habituation Gene Zebrafish Insulin-like growth factor 1 receptor 030304 developmental biology Neurons Genetics 0303 health sciences Behavior Animal General Neuroscience biology.organism_classification Cell biology Mutation Female Function (biology) 030217 neurology & neurosurgery Signal Transduction Genetic screen |
| Zdroj: | Neuron. 87:906-907 |
| ISSN: | 0896-6273 |
| Popis: | SummaryHabituation 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. |
| Databáze: | OpenAIRE |
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