Analysis of the interaction between DVAP, the orthologue of human VAPB, and Drosophila Sac1
نویسنده
چکیده
............................................................................................................. 3 Acknowledgements ............................................................................................ 5 Table of contents ................................................................................................ 6 Table of Figures ............................................................................................... 10 List of Tables .................................................................................................... 12 Abbreviations ................................................................................................... 13 Chapter 1: Introduction .................................................................................. 18 1.1 Neurodegenerative diseases ......................................................................... 18 1.2 Amyotrophic Lateral Sclerosis .................................................................... 19 1.3 Drosophila as a model organism to study neurodegeneration ..................... 23 1.3.1 The UAS/Gal4 system .............................................................................. 24 1.3.2 The Drosophila larval Neuromuscular Junction ....................................... 25 1.3.3 The adult Drosophila eye ......................................................................... 25 1.4 VAPBinduced Amyotrophic Lateral Sclerosis (ALS type 8) ................... 26 1.5 Vesicle-associated-membrane-protein(VAMP)/synaptobrevin associated proteins (VAPs) ................................................................................................. 27 1.5.1 VAP proteins are plasma-membrane-lipid sensors ................................... 32 1.5.2 VAP proteins and the Unfolded Protein Response ................................... 34 1.5.3 ALS8-causative mutations in hVAPB ...................................................... 34 1.6 Drosophila VAPB (DVAP) ........................................................................ 36 1.7 VAP interacting proteins ............................................................................. 37 1.8 Interaction between VAP and proteins involved in lipid metabolism and homeostasis ........................................................................................................ 38 1.8.1 VAP-interacting proteins not containing a FFAT motif in their sequence ........................................................................................................................... 38 1.8.2 VAP-interacting proteins containing a FFAT motif in their sequence ..... 46
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