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.
Tang
B L
BL
Membrane Biology Laboratory, National University of Singapore, Republic of Singapore.
Low
S H
SH
Hong
W
W
D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D006224:Cricetinae; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008970:Molecular Weight; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D000520:alpha-Glucosidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D005656:Fungal Proteins; D020662:Guanine Nucleotide Exchange Factors; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C071239:SEC12 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C042059:glucosidase I; D000520:alpha-Glucosidases; D018819:Dipeptidyl Peptidase 4