Advertisement

 

 

Contribution of the clathrin adaptor AP-1 subunit µ1 to acidic cluster protein sorting.

Contribution of the clathrin adaptor AP-1 subunit µ1 to acidic cluster protein sorting.
Author Information (click to view)

Navarro Negredo P, Edgar JR, Wrobel AG, Zaccai NR, Antrobus R, Owen DJ, Robinson MS,


Navarro Negredo P, Edgar JR, Wrobel AG, Zaccai NR, Antrobus R, Owen DJ, Robinson MS, (click to view)

Navarro Negredo P, Edgar JR, Wrobel AG, Zaccai NR, Antrobus R, Owen DJ, Robinson MS,

Advertisement
Share on FacebookTweet about this on TwitterShare on LinkedIn

The Journal of cell biology 2017 07 25() pii 10.1083/jcb.201602058

Abstract

Acidic clusters act as sorting signals for packaging cargo into clathrin-coated vesicles (CCVs), and also facilitate down-regulation of MHC-I by HIV-1 Nef. To find acidic cluster sorting machinery, we performed a gene-trap screen and identified the medium subunit (µ1) of the clathrin adaptor AP-1 as a top hit. In µ1 knockout cells, intracellular CCVs still form, but acidic cluster proteins are depleted, although several other CCV components were either unaffected or increased, indicating that cells can compensate for long-term loss of AP-1. In vitro experiments showed that the basic patch on µ1 that interacts with the Nef acidic cluster also contributes to the binding of endogenous acidic cluster proteins. Surprisingly, µ1 mutant proteins lacking the basic patch and/or the tyrosine-based motif binding pocket could rescue the µ1 knockout phenotype completely. In contrast, these mutants failed to rescue Nef-induced down-regulation of MHC class I, suggesting a possible mechanism for attacking the virus while sparing the host cell.

Submit a Comment

Your email address will not be published. Required fields are marked *

12 + 3 =

[ HIDE/SHOW ]