Sr. Caldwell et al., Degradation of endoplasmic reticulum (ER) quality control substrates requires transport between the ER and Golgi, J BIOL CHEM, 276(26), 2001, pp. 23296-23303
Endoplasmic reticulum (ER) quality control (ERQC) components retain and deg
rade misfolded proteins, and our results have found that the degradation of
the soluble ERQC substrates CPY* and PrA* but not membrane spanning ERQC s
ubstrates requires transport between the ER and Golgi. Stabilization of the
se misfolded soluble proteins was seen in cells lacking Erv29p, a probable
Golgi localized protein that cycles through the ER by means of a di-lysine
ER retrieval motif (KKKIY). Cells lacking Erv29p also displayed severely re
tarded ER exit kinetics for a subset of correctly folded proteins. We sugge
st that Erv29p is likely involved in cargo loading of a subset of proteins,
including soluble misfolded proteins, into vesicles for ER exit. The stabi
lization of soluble ERQC substrates in both erv29 Delta cells and sec mutan
ts blocked in either ER exit (sec12) or vesicle delivery to the Golgi (sec1
8) suggests that ER-Golgi transport is required for ERQC and reveals a new
aspect of the degradative mechanism.