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