title: Masking of an endoplasmic reticulum retention signal by its presence in the two subunits of the asialoglycoprotein receptor.
abstract: Human asialoglycoprotein receptor H1 and H2b subunits assemble into a hetero-oligomer that travels to the cell surface. The H2a variant on the other hand is a precursor of a cleaved soluble form that is secreted. Uncleaved H2a precursor molecules cannot exit the endoplasmic reticulum (ER), a lumenal juxtamembrane pentapeptide being responsible for their retention. Insertion of this pentapeptide into H1 (H1i5) causes its complete ER retention but not fast degradation as happens to H2a. Cotransfection of H2a elicited, by heterodimerization, the Golgi processing of H1i5 and its surface expression. This occurred to a much lesser extent by cotransfection of H2b. Likewise, coexpression of H1i5 and not H1 stabilized H2a and caused its export to the cell surface. Homodimerization of molecules containing the pentapeptide did not cancel the retention. Thus, only when the pentapeptide is present in both subunits is the ER retention efficiently abrogated. The results show the unexpected finding that identical ER retention signals present in two associated chains can mask and cancel each other's effect. This could have important implications as similar abrogation of ER retention of other proteins could eventually be obtained by engineering and coexpressing an associated protein containing the same retention signal.
authors.affiliation: Department of Cell Research, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Shenkman
authors.forename: M
authors.initials: M
authors.lastname: Ehrlich
authors.forename: G Z
authors.initials: GZ
authors.lastname: Lederkremer
mesh_terms: D016475:3T3 Cells; D000818:Animals; D037263:Asialoglycoprotein Receptor; D019281:Dimerization; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D051379:Mice; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D037263:Asialoglycoprotein Receptor; D011956:Receptors, Cell Surface