Drosophila Fatty Acid Transport Protein Regulates Rhodopsin-1 Metabolism and Is Required for Photoreceptor Neuron Survival

Abstract

Tight regulation of the visual response is essential for photoreceptor function and survival. Visual response dysregulation often leads to photoreceptor cell degeneration, but the causes of such cell death are not well understood. In this study, we investigated a fatty acid transport protein (fatp) null mutation that caused adult-onset and progressive photoreceptor cell death. Consistent with fatp having a role in the retina, we showed that fatp is expressed in adult photoreceptors and accessory cells and that its re-expression in photoreceptors rescued photoreceptor viability in fatp mutants. The visual response in young fatp-mutant flies was abnormal with elevated electroretinogram amplitudes associated with high levels of Rhodopsin-1 (Rh1). Reducing Rh1 levels in rh1 mutants or depriving flies of vitamin A rescued photoreceptor cell death in fatp mutant flies. Our results indicate that fatp promotes photoreceptor survival by regulating Rh1 abundance.

The Glia-Neuron Lactate Shuttle and Elevated ROS Promote Lipid Synthesis in Neurons and Lipid Droplet Accumulation in Glia via APOE/D

“…We therefore tested Fatp , the fly homolog of FATP1 (SLC27A1) and FATP4 (SLC27A4) (Dourlen et al, 2012; Dourlen et al, 2015). Finally, we assessed the function of various apolipoproteins that belong to the lipocalin family (Hauser et al, 2011; Kalaany and Mangelsdorf, 2006), such as glaz and nlaz .…”

“…These proteins are localized to the ER and plasma membrane in vertebrate cells (Stahl, 2004). Drosophila Fatp is expressed in both neurons and glia (Dourlen et al, 2012) and is most similar to mammalian FATP1 and FATP4 (Dourlen et al, 2015). We reduced expression of Fatp in neurons and glia and ascertained that these manipulations do not affect PR morphology immediately after eclosion (Figure S4A).…”

Flexible origin of hydrocarbon/pheromone precursors in Drosophila melanogaster

“…Previous Drosophila studies on fatp mutants reported metabolic and eye-specifi c phenotypes ( 32,33 ) but did not discriminate between FAtransporter or ACS activities. Importantly, our observations favor the notion that in the process of CHC synthesis, FATP acts instead through its ACS domain, because fatp knockdown impedes mbCHC synthesis in the oenocytes, and mbCHC precursors are mainly synthetized within the ( Fig.…”

The Tomato/GFP-FLP/FRT Method for Live Imaging of Mosaic Adult <em>Drosophila</em> Photoreceptor Cells

“…To date, only one mosaic screen has investigated the mechanisms regulating adult PR function, by monitoring the visual response via electroretinogram recordings 32 . With the Tomato/GFP-FLP/FRT method and the possibility of performing time course analysis in living mutant animals, we have designed a new method for identifying the factors regulating adult PR viability and function 20,24 .…”