1. COG7 deficiency in Drosophila generates multifaceted developmental, behavioral and protein glycosylation phenotypes
- Author
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Michael Tiemeyer, Roberta Fraschini, Katherine H. Tiemeyer, Angela Karimpour-Ghahnavieh, Tadahiro Kumagai, Sarah Baas Robinson, Anna Frappaolo, Giorgio Belloni, Roberto Piergentili, Stefano Sechi, Maria Grazia Giansanti, Frappaolo, A, Sechi, S, Kumagai, T, Robinson, S, Fraschini, R, Ghahnavieh, A, Belloni, G, Piergentili, R, Tiemeyer, K, Tiemeyer, M, and Giansanti, M more...
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0301 basic medicine ,enetic omplementation est ,post-translational ,Golgi Apparatus ,henotype ,biological transport ,chemistry.chemical_compound ,ncogene roteins ,0302 clinical medicine ,Golgi ,animal ,Golgi pparatus ,arva ,GOLPH3 ,Genetics ,Oncogene Proteins ,gait disorders ,neurologic ,drosophila proteins ,Gene Expression Regulation, Developmental ,protein processing ,rab GTP-binding proteins ,Phenotype ,Cell biology ,animals ,COG7 ,Larva ,symbols ,Golgi Phosphoprotein 3 ,Drosophila ,vesicular transport proteins ,Drosophila melanogaster ,Drosophila Protein ,Research Article ,evelopmental ,Glycosylation ,glycosylation ,Neuromuscular Junction ,euromuscular Junction ,cytokinesis ,BIO/18 - GENETICA ,Biology ,drosophila melanogaster ,03 medical and health sciences ,symbols.namesake ,Polysaccharides ,Humans ,olysaccharides ,Gait Disorders, Neurologic ,gene xpression egulation ,disease models ,gene deletion ,fungi ,Genetic Complementation Test ,RAB1 ,Cell Biology ,Golgi apparatus ,biology.organism_classification ,congenital disorders of glycosylation ,disease models, animal ,gait disorders, neurologic ,gene xpression egulation, evelopmental ,umans ,Mannose ,protein processing, post-translational ,Disease Models, Animal ,030104 developmental biology ,chemistry ,Protein Processing, Post-Translational ,030217 neurology & neurosurgery ,Cytokinesis - Abstract
Congenital Disorders of Glycosylation (CDG) comprise a family of human multi-systemic diseases caused by recessive mutations in genes required for protein N-glycosylation. More than 100 distinct forms of CDGs have been identified and most of them cause severe neurological impairment. The Conserved Oligomeric Golgi (COG) complex mediates tethering of vesicles carrying glycosylation enzymes across the Golgi cisternae. Mutations affecting human COG1, COG2, COG4-COG8 cause monogenic forms of inherited, autosomal recessive, CDGs. We have generated a Drosophila COG7-CDG model which closely parallels the pathological characteristics of COG7-CDG patients including pronounced neuromotor defects associated with altered N-glycome profiles. Consistent with these alterations, larval neuromuscular junctions of Cog7 mutants exhibit a significant reduction of bouton numbers. We further demonstrate that the COG complex cooperate with Rab1 and Golgi phosphoprotein 3, to regulate Golgi trafficking and that overexpression of Rab1 can rescue the cytokinesis defects and the locomotor defects associated with loss of Cog7. Our results altogether suggest that the Drosophila COG7-CDG model can be used to test novel potential therapeutic strategies by modulating trafficking pathways. more...
- Published
- 2017
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