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 nonglycosylated, dimeric, and hexameric type I membrane protein that has been established as a marker protein for a tubulovesicular intermediate compartment in which protein transport from the endoplasmic reticulum to the Golgi apparatus 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 cytoplasmically exposed COOH terminus. Here we report that overexpression of ERGIC-53 in COS cells saturates its intracellular retention system leading to the appearance of ERGIC-53 at the cell surface. Cell surface ERGIC-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 endocytosis.
Kappeler
F
F
Department of Pharmacology, University of Basel, Switzerland.
Itin
C
C
Schindler
R
R
Hauri
H P
HP
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D018076:DNA, Complementary / Q000378:metabolism; D004705:Endocytosis; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006056:Golgi Apparatus / Q000378:metabolism*; D007700:Kinetics; D008239:Lysine; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D012694:Serine; D014162:Transfection
D018076:DNA, Complementary; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins; D012694:Serine; D008239:Lysine