Anaplastic Lymphoma Kinase Acts in the Mushroom Body to Negatively Regulate Sleep

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Animal and human studies suggest that sleep has a profound impact on learning and memory. However, little is known about the molecular pathways linking these phenomena. We report that mutations in the Drosophila Anaplastic lymphoma kinase (Alk) gene, an ortholog of a human oncogene ALK, cause increased sleep. ALK is required for sleep suppression in the mushroom body, a structure important for both sleep and memory. ALK generally activates the Ras/ERK pathway, which is negatively regulated by Neurofibromin 1 (NF1). Mutations in Nf1 are the causes of the common neurological disorder Neurofibromatosis type 1 (NF1), which affects 1 in 3,000 live births. We find that male flies lacking the NF1 protein have reduced sleep, a phenotype opposite that of Alk flies. Interestingly, even though mutations in Nf1 don’t always cause short sleep in female flies, they suppress the sleep increase induced by ALK inactivation. Previous studies have shown that Alk and Nf1 play antagonistic roles in learning and that both genes regulate synaptic growth. Thus Alk and Nf1 interact to regulate both sleep and learning, suggesting that the two processes share a common pathway. Our results support a model in which changes in synaptic plasticity during sleep promote learning and memory.

Vyšlo v časopise: Anaplastic Lymphoma Kinase Acts in the Mushroom Body to Negatively Regulate Sleep. PLoS Genet 11(11): e32767. doi:10.1371/journal.pgen.1005611
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005611

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