Abstract
Though evidence is mounting that a major function of sleep is to maintain brain plasticity and consolidate memory, little is known about the molecular pathways by which learning and sleep processes intercept. Anaplastic lymphoma kinase (Alk), the gene encoding a tyrosine receptor kinase whose inadvertent activation is the cause of many cancers, is implicated in synapse formation and cognitive functions. In particular, Alk genetically interacts with Neurofibromatosis 1 (Nf1) to regulate growth and associative learning in flies. We show that Alk mutants have increased sleep. Using a targeted RNAi screen we localized the negative effects of Alk on sleep to the mushroom body, a structure important for both sleep and memory. We also report that mutations in Nf1 produce a sexually dimorphic short sleep phenotype, and suppress the long sleep phenotype of Alk. Thus Alk and Nf1 interact in both learning and sleep regulation, highlighting a common pathway in these two processes.
Highlights
Sleep behavior is conserved from worms and insects to fish and mammals [1]
We report that mutations in the Drosophila Anaplastic lymphoma kinase (Alk) gene, an ortholog of a human oncogene ALK, cause increased sleep
ALK generally activates the Ras/ERK pathway, which is negatively regulated by Neurofibromin 1 (NF1)
Summary
Sleep behavior is conserved from worms and insects to fish and mammals [1]. It is hypothesized that a major function of sleep is to maintain brain function, in particular, to ensure synaptic homeostasis of neurons and to consolidate memory [2,3]. Levels of synaptic proteins are associated with sleep/wake states in both flies and mammals [4,5], and sleep deprivation impairs memory formation in a variety of species, including humans [6], mice [7], and Drosophila [8,9]. Some molecules that regulate learning and memory turn out to be required for sleep/wake regulation [10]. Only a handful of such molecules have been identified and for most it is not known if effects on the two processes are mechanistically linked
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