title: The signal peptide of the rotavirus glycoprotein VP7 is essential for its retention in the ER as an integral membrane protein.
abstract: The rotavirus glycoprotein VP7 has a cleavable signal peptide and is normally resident as an integral membrane protein in the ER of infected cells. A gene was constructed in which the VP7 H2 signal peptide was replaced by one from influenza hemagglutinin. COS cells transfected with this gene produced VP7 with the correct amino terminus, but the protein was rapidly secreted. Uncleaved VP7 from either precursor was not detected in cells after brief pulse-labeling, suggesting that the signal peptide was not acting as a temporary anchor; rather, it exerted its effect despite rapid cleavage. By splicing the H2 signal peptide onto another reporter protein, the malaria S-antigen, we demonstrated that H2 was necessary, but not itself sufficient, for targeting and retention. We propose that an interaction between the cleaved signal peptide and other downstream sequences in VP7 is required for retention of this protein in the ER as an integral membrane polypeptide.
authors.affiliation: CSIRO Division of Biotechnology, Laboratory for Molecular Biology, North Ryde, New South Wales, Australia.
authors.forename: S C
authors.initials: SC
authors.lastname: Stirzaker
authors.forename: G W
authors.initials: GW
authors.lastname: Both
mesh_terms: D000818:Animals; D000956:Antigens, Viral; D001692:Biological Transport; D002213:Capsid / Q000378:metabolism*; D036022:Capsid Proteins; D002451:Cell Compartmentation; D002460:Cell Line; D004252:DNA Mutational Analysis; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals / Q000378:metabolism*; D012401:Rotavirus / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000956:Antigens, Viral; D036022:Capsid Proteins; D008562:Membrane Glycoproteins; D021382:Protein Sorting Signals; C050779:VP7 protein, Rotavirus