Differential fates of invertase mutants in the yeast endoplasmic reticulum

A number of proteins have been identified as substrates for endoplasmic ret iculum (ER)-associated protein degradation (ERAD) and we describe here a ne w model substrate with which to study this process. Two secretion-defective forms of yeast invertase that accumulated in the ER to greatly different l evels were examined: Suc2-538p levels were low, while Suc2-533p was present in high amounts. Because Suc2-533p and Suc2-538p mRNA levels were comparab le, we examined whether Suc2-538p was targeted for degradation. Both mutant polypeptide levels were unaffected in a yeast strain deficient in vacuolar protease activity and, additionally, we showed that Suc2-538p was stabiliz ed in ERAD-deficient strains, demonstrating that Suc2-538p was a substrate for ERAD. Copyright (C) 2000 John Wiley & Sons, Ltd.