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Eissenberg, J.C., Ilvarsonn, A.M., Sly, W.S., Waheed, A., Krzyzanek, V., Pohlmann, R., Waschkau, D., Kretzschmar, D., Dennes, A.C. (2011). Drosophila GGA Model: An Ultimate Gateway to GGA Analysis.  Traffic 12(12): 1821--1838.
FlyBase ID
FBrf0216574
Publication Type
Research paper
Abstract

Golgi-localized, γ-ear-containing, ADP ribosylation factor-binding (GGA) proteins are monomeric adaptors implicated in clathrin-mediated vesicular transport between the trans Golgi network and endosomes, characterized mainly from cell culture analysis of lysosomal sorting. To provide the first demonstration of GGA's role in vivo, we used Drosophila which has a single GGA and a single lysosomal sorting receptor, lysosomal enzyme receptor protein (LERP). Using RNAi knockdowns, we show that the Drosophila GGA is required for lysosomal sorting. We further identified authentic components of the Drosophila lysosomal sorting system--the sorting receptor LERP, the sorting adaptor GGA and the lysosomal cargo cathepsins B1, D and L--to show that GGA depletion results in lysosomal dysfunction. Abnormal lysosomal morphology, missorting of lysosomal cathepsins and impaired lysosomal proteolysis show disturbed LERP trafficking after GGA depletion. GGA is highly expressed in the mushroom bodies and the pigment cells of the retina, and increasing or decreasing the levels of GGA in the eyes leads to retinal defects. Reduced GGA levels also enhance an eye defect caused by overexpression of the autophagy-associated protein Blue cheese (Bchs), implicating GGA in autophagic processes. This shows that Drosophila provides an excellent whole-animal model to gain new insights into the function of GGA in the physiological environment of a multicellular organism.

PubMed ID
PubMed Central ID
PMC3601743 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Traffic
    Title
    Traffic
    Publication Year
    2000-
    ISBN/ISSN
    1398-9219
    Data From Reference