Critical role of calnexin in Nef- mediated inactivation of ABCA1 Lucas T. Jennelle and Michael I. Bukrinsky Nef reduces cholesterol efflux and ABCA1 protein levels ABCA1 Interacts with Calnexin Calnexin Knockout Allows ABCA1 to Escape from ER ABCA1-GFPCo-LocalizationDsRed2-ER CANX siRNA CNTL siRNA DEF GHI ER X Nef Inhibits Interaction between ABCA1 and Calnexin ABCA1 Co-Localizes with Calnexin and Nef Reduces Co-Localization ABCA1-GFPDsRed2-CANXCo-LocalizationOverlay DEFG HIJK WT Nef Control ER Nef Interacts With Calnexin Conclusion: Mechanism of Nef Action Final ABCA1 structure is Not properly folded and cannot mediate cholesterol efflux Acknowledgements Supported by NIH grants R01 HL093818, R21 DK and R03 TW006238