iFly: The eye of the fruit fly as a model to study autophagy and related trafficking pathways
Section snippets
Overview of autophagy
Autophagy is a highly conserved catabolic process of eukaryotic cells, which is responsible for the turnover of cytoplasmic material via the lysosomal apparatus. Autophagy has three subtypes: macroautophagy, microautophagy, and chaperone mediated autophagy (Mizushima et al., 2008). Of these pathways, the first one is the best characterized, so we will focus on macroautophagy (hereafter simply referred to as autophagy) in this review.
The autophagic process begins with the emergence of a double
The structure and development of the Drosophila compound eye
The compound eye of the fly develops from the larval eye primordium, the so-called eye-antennal disc (Fig. 1A). This small, paired organ belongs to the group of imaginal discs that all consist of two epithelial monolayers opposing each other. One cell layer of a disc is a squamous epithelium and it is called the peripodial membrane, and the other layer is a columnar epithelium, the so-called disc proper. Besides its structural role, the function of the peripodial membrane is to secrete
Studying autophagy in the Drosophila eye
Much of the work on autophagy was carried out in the polyploid larval fat body in Drosophila, as both starvation-induced and developmental forms of this process can be easily studied in that tissue (Mauvezin et al., 2014, Nagy et al., 2014). The level of autophagy is relatively low in larval eye discs or adult eyes, and the loss of autophagy genes does not alter the structure of the compound eye (Juhasz et al., 2007, Velentzas et al., 2013) (Fig. 3D). The precisely controlled activity of
The Drosophila eye as a tool to study the role of autophagy in models of proteinopathy and neurodegeneration
Retinule cells are primary sensory neurons, so the fly eye is widely used to study the mechanisms of neurodegeneration. Most human diseases have a Drosophila model, and as working with fruit flies is faster and often easier than with mammals thanks to the shorter lifecycle and less genetic redundancy, researchers have much more room to maneuver when it comes to examine models of neurodegenerative disorders (Ambegaokar et al., 2010, Rincon-Limas et al., 2012). Neurodegeneration can be relatively
Autophagy prevents light-induced retinal degeneration in Drosophila
The fly eye also proved to be useful to study retinopathies, and many retinal disease model flies are available by now (Knust, 2007). The pathomechanisms of retinal degenerative disorders are extremely diverse, but in most cases it is the misfolded or mutated form of Rhodopsin that causes retinal cell death. One example is the inheritable disease retinitis pigmentosa (RP), a form of retinopathy characterized by progressive photoreceptor loss mostly due to mutations affecting Rhodopsin. The
Connections between pigment granule synthesis and autophagy
Ommatidia in the fly eye are isolated by pigment cells, and pigment granules are lysosome-related organelles, so the Drosophila eye is excellent for the study of biosynthetic lysosomal trafficking (Lloyd et al., 1998, Shoup, 1966). Recent studies show that several genes affecting pigment granule biosynthesis also have a role in lysosome biogenesis, so these are important for autophagic degradation as well. For example, one abnormal eye color phenotype is caused by a mutation in mauve (mv), the
Concluding remarks
To summarize the role of autophagy in the fruit fly eye, we can conclude that while it is dispensable for pigment granule synthesis and eye development, autophagy is important for maintaining retinal homeostasis. Thus, the Drosophila retina provides an ideal tool to study the involvement of autophagy and autophagy-related genes in certain diseases including proteinopathies and retinopathies. Established neurodegeneration model flies can be used for the screening of relevant genes and
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