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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. D. E. F. CNTL siRNA. CANX siRNA. G. H. - PowerPoint PPT Presentation
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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-GFP Co-LocalizationDsRed2-ER
CANX
siRN
ACN
TL si
RNA D E F
G H I
ER X
Nef Inhibits Interaction between ABCA1 and Calnexin
ABCA1 Co-Localizes with Calnexinand Nef Reduces Co-Localization
ABCA1-GFP DsRed2-CANX Co-Localization Overlay
D E F G
H I J K
WT
Nef
Cont
rol
ER 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 DK072926 and R03 TW006238