Sorting of Oligomerized Proteins: Implications in Toxin Trafficking and Quality Control
نویسندگان
چکیده
................................................................................................................................. 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
منابع مشابه
Manganese induces oligomerization to promote down-regulation of the intracellular trafficking receptor used by Shiga toxin
Manganese (Mn) protects cells against lethal doses of purified Shiga toxin by causing the degradation of the cycling transmembrane protein GPP130, which the toxin uses as a trafficking receptor. Mn-induced GPP130 down-regulation, in addition to being a potential therapeutic approach against Shiga toxicosis, is a model for the study of metal-regulated protein sorting. Significantly, however, the...
متن کاملFamily-wide characterization of the DENN domain Rab GDP-GTP exchange factors
A key requirement for Rab function in membrane trafficking is site-specific activation by GDP-GTP exchange factors (GEFs), but the majority of the 63 human Rabs have no known GEF. We have performed a systematic characterization of the 17 human DENN domain proteins and demonstrated that they are specific GEFs for 10 Rabs. DENND1A/1B localize to clathrin patches at the plasma membrane and activat...
متن کاملManganese-induced trafficking and turnover of GPP130 is mediated by sortilin
Elevated, nontoxic doses of manganese (Mn) protect against Shiga toxin-1-induced cell death via down-regulation of GPP130, a cycling Golgi membrane protein that serves as an endosome-to-Golgi trafficking receptor for the toxin. Mn binds to GPP130 in the Golgi and causes GPP130 to oligomerize/aggregate, and the complexes are diverted to lysosomes. In fact, based on experiments using the self-int...
متن کاملAGAP2 regulates retrograde transport between early endosomes and the TGN.
The retrograde transport route links early endosomes and the TGN. Several endogenous and exogenous cargo proteins use this pathway, one of which is the well-explored bacterial Shiga toxin. ADP-ribosylation factors (Arfs) are approximately 20 kDa GTP-binding proteins that are required for protein traffic at the level of the Golgi complex and early endosomes. In this study, we expressed mutants a...
متن کاملRecombinant Production of a Novel Fusion Protein: Listeriolysin O Fragment Fused to S1 Subunit Of Pertussis Toxin
Background: Some resources have suggested that genetically inactivated pertussis toxoid (PTs) bear a more protective effect than chemically inactivated products. This study aimed to produce new version of PT, by cloning an inactive pertussis toxin S1 subunit (PTS1) in a fusion form with N-terminal half of the listeriolysin O (LLO) pore-forming toxin. Methods: Deposited pdb structure file of the...
متن کامل