Abstract
The protein O-glucosyltransferase Rumi/POGLUT1 regulates Drosophila Notch signaling by adding O-glucose residues to the Notch extracellular domain. Rumi has other predicted targets including Crumbs (Crb) and Eyes shut (Eys), both of which are involved in photoreceptor development. However, whether Rumi is required for the function of Crb and Eys remains unknown. Here we report that in the absence of Rumi or its enzymatic activity, several rhabdomeres in each ommatidium fail to separate from one another in a Notch-independent manner. Mass spectral analysis indicates the presence of O-glucose on Crb and Eys. However, mutating all O-glucosylation sites in a crb knock-in allele does not cause rhabdomere attachment, ruling out Crb as a biologically-relevant Rumi target in this process. In contrast, eys and rumi exhibit a dosage-sensitive genetic interaction. In addition, although in wild-type ommatidia most of the Eys protein is found in the inter-rhabdomeral space (IRS), in rumi mutants a significant fraction of Eys remains in the photoreceptor cells. The intracellular accumulation of Eys and the IRS defect worsen in rumi mutants raised at a higher temperature, and are accompanied by a ∼50% decrease in the total level of Eys. Moreover, removing one copy of an endoplasmic reticulum chaperone enhances the rhabdomere attachment in rumi mutant animals. Altogether, our data suggest that O-glucosylation of Eys by Rumi ensures rhabdomere separation by promoting proper Eys folding and stability in a critical time window during the mid-pupal stage. Human EYS, which is mutated in patients with autosomal recessive retinitis pigmentosa, also harbors multiple Rumi target sites. Therefore, the role of O-glucose in regulating Eys may be conserved.
Highlights
Diurnal insects possess ‘‘apposition eyes’’ in which ommatidia are optically isolated from each other [1,2]
We have previously shown that an enzyme called Rumi adds glucose molecules to an important cell surface receptor called Notch, and that glucose plays a key role in the function of Notch both in fruit flies and in mammals
We have identified a new Rumi target called ‘‘Eyes shut’’, a secreted protein with a critical role in the optical isolation of neighboring photoreceptors in the fly eye
Summary
Diurnal insects possess ‘‘apposition eyes’’ in which ommatidia are optically isolated from each other [1,2]. A modification of the apposition eye arose during insect evolution in dipteran flies, where an extracellular lumen called the inter-rhabdomeral space (IRS) forms to separate and optically isolate the rhabdomeres in each ommatidium from one another. Due to this structural modification and the accompanying regrouping of photoreceptor axons among neighboring ommatidia, information from photoreceptor cells that receive light from the same point in the space merge on the same postsynaptic targets in the lamina [3]. This type of eye is referred to as a neural superposition eye, and these improvements allow for increased light sensitivity without sacrificing resolution [1,4]
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