Bai Lei, Sehgal Amita
Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
PLoS Genet. 2015 Nov 4;11(11):e1005611. doi: 10.1371/journal.pgen.1005611. eCollection 2015 Nov.
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.
尽管越来越多的证据表明睡眠的一个主要功能是维持大脑可塑性和巩固记忆，但对于学习和睡眠过程相互交织的分子途径却知之甚少。间变性淋巴瘤激酶（Alk），一种编码酪氨酸受体激酶的基因，其意外激活是许多癌症的病因，它与突触形成和认知功能有关。特别是，Alk在基因层面与神经纤维瘤病1型（Nf1）相互作用，以调节果蝇的生长和联想学习。我们发现Alk突变体的睡眠时间增加。通过靶向RNA干扰筛选，我们将Alk对睡眠的负面影响定位到蘑菇体，这是一个对睡眠和记忆都很重要的结构。我们还报告说，Nf1的突变产生了一种性别二态性的短睡眠表型，并抑制了Alk的长睡眠表型。因此，Alk和Nf1在学习和睡眠调节中相互作用，突出了这两个过程中的共同途径。
