................................................................................................................................. 4 ACKNOWLEDGEMENTS .......................................................................................................... 6 INTRODUCTION ........................................................................................................................ 8 1.1 LYSOSOMAL DEGRADATION AS A MEANS OF GOLGI QUALITY CONTROL ............ 10 1.1.1 Integral membrane proteins ........................................................................................................ 10 1.1.2 Soluble proteins ................................................................................................................................. 15 1.1.3 Induced Oligomers ............................................................................................................................ 17 1.2 AUTOPHAGY AS A MEANS OF GOLGI QUALITY CONTROL .......................................... 23 1.3 PROTEASOMAL DEGRADATION AS A MEANS OF GOLGI QUALITY CONTROL ...... 26 1.4 CONCLUSION ............................................................................................................................. 27 MANGANESE-INDUCED TRAFFICKING AND TURNOVER OF GPP130 IS MEDIATED BY SORTILIN ..................................................................................................... 29 2.1 ABSTRACT ................................................................................................................................. 29 2.2 INTRODUCTION ....................................................................................................................... 30 2.3 RESULTS ..................................................................................................................................... 33 2.4 DISCUSSION ............................................................................................................................... 50 2.5 MATERIALS AND METHODS ................................................................................................. 54 CONCLUSIONS AND FUTURE DIRECTIONS .................................................................... 60 3.1 CONCLUSIONS ........................................................................................................................... 60 3.2 FUTURE DIRECTIONS ............................................................................................................. 63 REFERENCES ............................................................................................................................ 68