Endoplasmic reticulum retention mediated by the transmembrane domain of type II membrane proteins Sec12p and glucosidase 1.

The yeast Sec12p, a type II protein localized to the yeast endoplasmic reticulum (ER), is similarly localized to the ER when expressed in mammalian cells. Replacing the transmembrane domain of the plasma membrane molecule dipeptidyl peptidase IV (D4) with that of Sec12p or the ER-localized enzyme glucosidase 1 resulted in the ER retention of the chimeric molecules, as assessed by immunocytochemical localization and the persistence of pulse-labeled proteins in the endoglycosidase H-sensitive form. Retention is not due to gross misfolding as these chimeras remained enzymatically active. Density gradient analysis revealed that the ER-localized chimeric molecules form high molecular weight oligomers quickly after synthesis. The type II transmembrane domain of ER proteins could therefore mediate retention in the ER.