Abstract
We show that a sleep-regulating, Ig-domain protein (NKT) is secreted from Drosophila mushroom body (MB) α'/β' neurons to act locally on other MB cell types. Pan-neuronal or broad MB expression of membrane-tethered NKT (tNkt) protein reduced sleep, like that of an NKT null mutant, suggesting blockade of a receptor mediating endogenous NKT action. In contrast, expression in neurons requiring NKT (the MB α'/β' cells), or non-MB sleep-regulating centers, did not reduce night sleep, indicating the presence of a local MB sleep-regulating circuit consisting of communicating neural subtypes. We suggest that the leucocyte-antigen-related like (Lar) transmembrane receptor may mediate NKT action. Knockdown or overexpression of Lar in the MB increased or decreased sleep, respectively, indicating the receptor promotes wakefulness. Surprisingly, selective expression of tNkt or knockdown of Lar in MB wake-promoting cells increased rather than decreased sleep, suggesting that NKT acts on wake- as well as sleep-promoting cell types to regulate sleep.