Intracellular transport of soluble and membrane-bound glycoproteins: Folding, assembly and secretion of anchor-free influenza hemagglutinin

I. Singh, R. W. Doms, K. R. Wagner, A. Helenius

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

The influenza hemagglutinin precursor (HA0) and many other glycoproteins fold and oligomerize in the endoplasmic reticulum (ER). Only correctly folded oligomers are transported to the cell surface. To analyse the rules which determine this type of ER sorting, we have extended our analysis of hemagglutinin transport to two soluble, anchor-free recombinant HA0s derived from X31/A/Aichi/68 and A/Japan/305/57 influenza A. The results showed that individual monomers rapidly acquired a folded structure similar to that of monomeric membrane-anchored HA0. They were efficiently transported and secreted, but oligomerization was not required for secretion. Trimers or higher order complexes were either not formed (X31 HA0), or appeared during passage through the late compartments of the secretory pathway, with no effect on the rate of transport (Japan HA0). However, when initial folding was disturbed by inhibition of N-linked glycosylation, anchor-free X31 HA0 was misfolded and retained in the ER as disulfide-linked complexes associated with binding protein, BiP (GRP78). The complexes were similar to those seen for the non-glycosylated membrane-bound HA0, but instead of forming immediately after synthesis they appeared with a half-time of 6 min. Taken together, the data demonstrate that the structural criteria that makes the anchor-free HA0 transport competent are less stringent than those for the membrane form; they must fold correctly but do not need to oligomerize.

Original languageEnglish (US)
Pages (from-to)631-639
Number of pages9
JournalEMBO Journal
Volume9
Issue number3
DOIs
StatePublished - 1990
Externally publishedYes

Keywords

  • anchor-free glycoprotein/BiP/endoplasmic reticulum
  • influenza hemagglutinin
  • intracellular transport
  • oligomerization

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint

Dive into the research topics of 'Intracellular transport of soluble and membrane-bound glycoproteins: Folding, assembly and secretion of anchor-free influenza hemagglutinin'. Together they form a unique fingerprint.

Cite this