Drosophila GGA Model: An Ultimate Gateway to GGA Analysis
| Autor: | André Dennes, Abdul Waheed, Regina Pohlmann, Doris Kretzschmar, Joel C. Eissenberg, Anne M. Ilvarsonn, Daniela Waschkau, Vladislav Krzyzanek, William S. Sly |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Endosome
Golgi Apparatus Nerve Tissue Proteins Endosomes Biology Biochemistry Clathrin Retina Article symbols.namesake Structural Biology Lysosome Genetics medicine Animals Drosophila Proteins Transport Vesicles Molecular Biology Lysosome-Associated Membrane Glycoproteins Cell Biology Golgi apparatus Cathepsins Cell biology Transport protein Vesicular transport protein Adaptor Proteins Vesicular Transport Protein Transport Phenotype medicine.anatomical_structure Gene Knockdown Techniques Proteolysis biology.protein symbols Drosophila RNA Interference Lysosomes Lerp Drosophila Protein trans-Golgi Network |
| Zdroj: | Traffic. 12:1821-1838 |
| ISSN: | 1398-9219 |
| DOI: | 10.1111/j.1600-0854.2011.01285.x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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