The Drosophila melanogaster Phospholipid Flippase dATP8B Is Required for Odorant Receptor Function

Abstract

The olfactory systems of insects are fundamental to all aspects of their behaviour, and insect olfactory receptor neurons (ORNs) exhibit exquisite specificity and sensitivity to a wide range of environmental cues. In Drosophila melanogaster, ORN responses are determined by three different receptor families, the odorant (Or), ionotropic-like (IR) and gustatory (Gr) receptors. However, the precise mechanisms of signalling by these different receptor families are not fully understood. Here we report the unexpected finding that the type 4 P-type ATPase phospholipid transporter dATP8B, the homologue of a protein associated with intrahepatic cholestasis and hearing loss in humans, is crucial for Drosophila olfactory responses. Mutations in dATP8B severely attenuate sensitivity of odorant detection specifically in Or-expressing ORNs, but do not affect responses mediated by IR or Gr receptors. Accordingly, we find dATP8B to be expressed in ORNs and localised to the dendritic membrane of the olfactory neurons where signal transduction occurs. Localisation of Or proteins to the dendrites is unaffected in dATP8B mutants, as is dendrite morphology, suggesting instead that dATP8B is critical for Or signalling. As dATP8B is a member of the phospholipid flippase family of ATPases, which function to determine asymmetry in phospholipid composition between the outer and inner leaflets of plasma membranes, our findings suggest a requirement for phospholipid asymmetry in the signalling of a specific family of chemoreceptor proteins.

Specialized odorant receptors in social insects that detect cuticular hydrocarbon cues and candidate pheromones

“…1b–e ). As done in previous studies, we heated the delivery cartridge for ~1 s (112.5 ± 2.8 °C, n = 10) with a butane torch to facilitate the volatilization of the stimulus and applied a 1 s pulse via a humidified airflow over the HsOr -expressing fly antenna 20 , 23 , 24 . In these studies, triacontane (C30), a hydrocarbon present on the H. saltator cuticle 13 , elicited robust and dose-dependent responses in HsOr281-expressing ab2A neurons, whereas other alkanes elicited little activity (Fig.…”

Perinatal exposure to diets with different n-6:n-3 fatty acid ratios affects olfactory tissue fatty acid composition

“…However, some observations support this idea. First, a member of the phospholipid flippase family has been shown to be essential for odourant receptor responses in Drosophila melanogaster 44,45 , suggesting that the PL composition of the OSN plasma membrane is an important factor for olfactory signalling. A number of studies also demonstrated that DHA-rich retinal PLs enhance the activity of rhodopsin, a receptor that belongs to the same G-protein-coupled receptor class as odourant receptors [46][47][48][49][50][51][52][53] .…”

Calmodulin Affects Sensitization of Drosophila melanogaster Odorant Receptors

“…Interestingly, the dATP8B phospholipid flippase was shown to be essential for an appropriate sensitivity of ORs, but not of IRs. It has been shown that mutation in the dATP8B gene strongly reduces the sensitivity of OR-expressing neurons (Liu et al, 2014 ). Understanding the basis and the molecular mechanism of insect OR sensitization relies on the knowledge of further regulators of sensitivity.…”