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PMID: 2557352 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Intracellular maturation and transport of the SV5 type II glycoprotein hemagglutinin-neuraminidase: specific and transient association with GRP78-BiP in the endoplasmic reticulum and extensive internalization from the cell surface.

The Journal of cell biology ·Vol. 109 ·No. 6 Pt 2 ·1989-12-00 ·Pages 3273-89

Ng DT, Randall RE, Lamb RA

Abstract

The hemagglutinin-neuraminidase (HN) glycoprotein of the paramyxovirus SV5 is a type II integral membrane protein that is expressed at the infected cell surface. The intracellular assembly and transport of HN in CV1 cells was examined using conformation-specific HN mAbs and sucrose density sedimentation analysis. HN was found to oligomerize with a t1/2 of 25-30 min and these data suggest the oligomer is a tetramer consisting primarily of two noncovalently associated disulfide-linked dimers. As HN oligomers could be found that were sensitive to endoglycosidase H digestion and oligomers formed in the presence of the ER to the Golgi complex transport inhibitor, carbonylcyanide m-chlorophenylhydrazone (CCCP), these data are consistent with HN oligomerization occurring in the ER. Unfolded or immature HN molecules that could not be recognized by conformation-specific antibodies were found to specifically associate with the resident ER protein GRP78-BiP. Immunoprecipitation of BiP-HN complexes with an immunoglobulin heavy-chain binding protein (BiP) antibody indicated that newly synthesized HN associated and dissociated from GRP78-BiP (t1/2 20-25 min) in an inverse correlation with the gain in reactivity with a HN conformation-specific antibody, suggesting that the transient association of GRP78-BiP with immature HN is part of the normal HN maturation pathway. After pulse-labeling of HN in infected cells, it was found that HN is rapidly turned over in cells (t1/2 2-2.5 h). This led to the finding that the vast majority of HN expressed at the cell surface, rather than being incorporated into budding virions, is internalized and degraded after localization to endocytic vesicles and lysosomes.

MeSH Terms
Animals Carrier Proteins/metabolism Cell Line Electrophoresis, Polyacrylamide Gel Endoplasmic Reticulum/metabolism Endoplasmic Reticulum Chaperone BiP Exocytosis HN Protein/metabolism Heat-Shock Proteins Lysosomes/metabolism Membrane Proteins/metabolism Mice Molecular Chaperones Oligopeptides/biosynthesis Parainfluenza Virus 1, Human/metabolism Protein Conformation Rabbits
Chemicals
Carrier Proteins Endoplasmic Reticulum Chaperone BiP HN Protein HSPA5 protein, human Heat-Shock Proteins Hspa5 protein, mouse Membrane Proteins Molecular Chaperones Oligopeptides
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Ng D T
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208-3500.
Randall R E
Lamb R A
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.109.6.3273
Published
1989-12-00
Pages
3273-89
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2115940
Subset
IM
Grants
NIAID NIH HHS · AI-20201 · United States
NIAID NIH HHS · AI-23173 · United States
NIGMS NIH HHS · GM-08061 · United States
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1083/jcb.109.6.3273 PMC Full Text View journal details
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