A DUAL ROLE FOR COOH-TERMINAL LYSINE RESIDUES IN PRE-GOLGI RETENTION AND ENDOCYTOSIS OF ERGIC-53

ERGIC-53 (former designation, p53) is a 53-kDa non-glycosylated, dimer ic, and hexameric type I membrane protein that has been established as a marker protein for a tubulovesicular intermediate compartment in wh ich protein transport from the endoplasmic reticulum to the Golgi appa ratus is blocked at 15 degrees C. Although ERGIC-53 is not a resident protein of the rough endoplasmic reticulum its cDNA sequence carries a double lysine endoplasmic reticulum retention motif at the cytoplasmi cally exposed COOH terminus. Here we report that overexpression of ERG IC-53 in COS cells saturates its intracellular retention system leadin g to the appearance of ERGIC-53 at the cell surface. Cell surface ERGI C-53 is efficiently endocytosed by a mechanism that is disturbed when the two critical lysines of the endoplasmic reticulum retention motif are replaced by serines. The results suggest a mechanistic similarity of pre-Golgi retention by the double lysine motif and lysine based. en docytosis.