Published online 22 October 2001. doi:10.1083/jcb1553iti2
© The Rockefeller University Press,
0021-9525/2001/10/322-a $5.00
The Journal of Cell Biology, Volume 155, Number 3, October 29, 2001 322-a-323
Shape up or ship out
| |
Some unfolded proteins cycle before being degraded.
|
|
When proteins become misfolded in the ER, a quality control system targets them to the cytoplasm for degradation. On page 355, Vashist et al. have uncovered two separate sorting systems involved in ER quality control, and have identified a novel gene required for one of the two pathways. The findings indicate that ER quality control is more complex than previously believed.
By tracking the fates of several mutant proteins in Saccharomyces cerevisiae, the authors identified a sorting step in the ER in which misfolded proteins are targeted to one of two pathways. Some proteins are packaged into COPII transport vesicles, while others are excluded from vesicles and retained in the ER. Proteins packaged into vesicles are transported to the Golgi apparatus, then returned to the ER by retrograde transport, at which point the two pathways converge and both the retained and retrieved proteins are degraded.
Each mutant protein only follows one pathway, suggesting that the sorting system is highly selective. Although the results are consistent with a model in which membrane proteins are retained while soluble proteins follow the retrieval pathway, the authors stress that more extensive analysis will be required to identify the preferences of the sorting system.A genetic screen uncovered a mutant allele of the BST1 gene that blocks the transport of misfolded proteins from the ER to the Golgi without affecting most normal protein transport. Although the retrieval pathway is blocked in these cells, proteins targeted to the retention pathway by the ER are still degraded normally. Vashist et al. are now identifying additional genes specifically involved in the retention and retrieval pathways. 
Alan W. Dove
alanwdove{at}earthlink.net
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
