AUTHOR=Kobayashi Riho , Nakane Shin , Tomita Jun , Funato Hiromasa , Yanagisawa Masashi , Kume Kazuhiko 

TITLE=A phosphorylation-deficient mutant of Sik3, a homolog of Sleepy, alters circadian sleep regulation by PDF neurons in Drosophila

JOURNAL=Frontiers in Neuroscience

VOLUME=17

YEAR=2023

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2023.1181555

DOI=10.3389/fnins.2023.1181555

ISSN=1662-453X

ABSTRACT=<p>Sleep behavior has been observed from non-vertebrates to humans. <italic>Sleepy</italic> mutation in mice resulted in a notable increase in sleep and was identified as an exon-skipping mutation of the <italic>salt-inducible kinase 3 (Sik3)</italic> gene, conserved among animals. The skipped exon includes a serine residue that is phosphorylated by protein kinase A. Overexpression of a mutant gene with the conversion of this serine into alanine (<italic>Sik3-SA</italic>) increased sleep in both mice and the fruit fly <italic>Drosophila melanogaster</italic>. However, the mechanism by which <italic>Sik3-SA</italic> increases sleep remains unclear. Here, we found that <italic>Sik3-SA</italic> overexpression in all neurons increased sleep under both light–dark (LD) conditions and constant dark (DD) conditions in <italic>Drosophila</italic>. Additionally, overexpression of <italic>Sik3-SA</italic> only in PDF neurons, which are a cluster of clock neurons regulating the circadian rhythm, increased sleep during subjective daytime while decreasing the amplitude of circadian rhythm. Furthermore, suppressing <italic>Sik3-SA</italic> overexpression specifically in PDF neurons in flies overexpressing <italic>Sik3-SA</italic> in all neurons reversed the sleep increase during subjective daytime. These results indicate that <italic>Sik3-SA</italic> alters the circadian function of PDF neurons and leads to an increase in sleep during subjective daytime under constant dark conditions.</p>