TY - JOUR
T1 - Drosophila GGA Model
T2 - An Ultimate Gateway to GGA Analysis
AU - Eissenberg, Joel C.
AU - Ilvarsonn, Anne M.
AU - Sly, William S.
AU - Waheed, Abdul
AU - Krzyzanek, Vladislav
AU - Pohlmann, Regina
AU - Waschkau, Daniela
AU - Kretzschmar, Doris
AU - Dennes, André C.
PY - 2011/12
Y1 - 2011/12
N2 - 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.
AB - 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.
KW - Clathrin adaptor
KW - GGA
KW - Lysosome
UR - http://www.scopus.com/inward/record.url?scp=81055140224&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=81055140224&partnerID=8YFLogxK
U2 - 10.1111/j.1600-0854.2011.01285.x
DO - 10.1111/j.1600-0854.2011.01285.x
M3 - Article
C2 - 21923734
AN - SCOPUS:81055140224
SN - 1398-9219
VL - 12
SP - 1821
EP - 1838
JO - Traffic
JF - Traffic
IS - 12
ER -