title: An alternatively spliced miniexon alters the subcellular fate of the human asialoglycoprotein receptor H2 subunit. Endoplasmic reticulum retention and degradation or cell surface expression.
abstract: Two types of cDNAs encoding the H2 subunit of the human asialoglycoprotein receptor had been cloned, differing only by the presence (H2a) or absence (H2b) of a segment of 15 base pairs (bp), encoding five amino acids (Glu-Gly-His-Arg-Gly) immediately carboxylterminal (exoplasmic) to the single membrane-spanning segment. We have cloned and sequenced this region of the H2 gene and showed that the two H2 forms are alternatively spliced variants differing in the presence of a 15-bp miniexon. Both H2 messenger RNAs were found in HepG2 cells, H2b accounting for about 92% of the H2 mRNAs. When expressed in NIH 3T3 cells without the H1 receptor subunit, the two-variant polypeptides exhibit different subcellular fates. H2a is completely retained in and degraded in the endoplasmic reticulum or a related pre-Golgi compartment. In contrast a substantial amount of H2b is processed by Golgi enzymes and reaches the cell surface. Thus, the sole difference determining the subcellular localization of the two forms if the five-amino acid insert in H2a. When a virion-packaged retroviral vector containing H2a cDNA infected 3T3 cells, 70% of the resulting clones expressed H2b and 30% H2a. Thus the 15-bp H2a miniexon can be spliced out, at least during the retrovirus life cycle.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142.
authors.forename: G Z
authors.initials: GZ
authors.lastname: Lederkremer
authors.forename: H F
authors.initials: HF
authors.lastname: Lodish
mesh_terms: D000595:Amino Acid Sequence; D037263:Asialoglycoprotein Receptor; D001483:Base Sequence; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons; D006801:Humans; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D037263:Asialoglycoprotein Receptor; D012333:RNA, Messenger; D011971:Receptors, Immunologic