title: The unique GGA clathrin adaptor of Drosophila melanogaster is not essential.
abstract: The Golgi-localized, γ-ear-containing, ARF binding proteins (GGAs) are a highly conserved family of monomeric clathrin adaptor proteins implicated in clathrin-mediated protein sorting between the trans-Golgi network and endosomes. GGA RNAi knockdowns in Drosophila have resulted in conflicting data concerning whether the Drosophila GGA (dGGA) is essential. The goal of this study was to define the null phenotype for the unique Drosophila GGA. We describe two independently derived dGGA mutations. Neither allele expresses detectable dGGA protein. Homozygous and hemizygous flies with each allele are viable and fertile. In contrast to a previous report using RNAi knockdown, GGA mutant flies show no evidence of age-dependent retinal degeneration or cathepsin missorting. Our results demonstrate that several of the previous RNAi knockdown phenotypes were the result of off-target effects. However, GGA null flies are hypersensitive to dietary chloroquine and to starvation, implicating GGA in lysosomal function and autophagy.
authors.affiliation: Department of Biology, Macelwane Hall, Saint Louis University, St. Louis, Missouri, USA.
authors.forename: Shan
authors.initials: S
authors.lastname: Luan
authors.forename: Anne M
authors.initials: AM
authors.lastname: Ilvarsonn
authors.forename: Joel C
authors.initials: JC
authors.lastname: Eissenberg
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000235:genetics; D002738:Chloroquine / Q000494:pharmacology; D002966:Clathrin / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D055785:Gene Knockdown Techniques; D057898:Hemizygote; D006720:Homozygote; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009154:Mutation; D010641:Phenotype; D034741:RNA, Small Interfering / Q000235:genetics; D013217:Starvation / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D015996:Survival Rate; D021601:trans-Golgi Network / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D002966:Clathrin; D029721:Drosophila Proteins; C407306:GGA adaptor proteins; D034741:RNA, Small Interfering; D002738:Chloroquine