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PMID: 10233156 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The secretory route of the leaderless protein interleukin 1beta involves exocytosis of endolysosome-related vesicles.

Molecular biology of the cell ·Vol. 10 ·No. 5 ·1999-05-00 ·Pages 1463-75

Andrei C, Dazzi C, Lotti L, Torrisi MR, Chimini G, Rubartelli A

Abstract

Interleukin 1beta (IL-1beta), a secretory protein lacking a signal peptide, does not follow the classical endoplasmic reticulum-to-Golgi pathway of secretion. Here we provide the evidence for a "leaderless" secretory route that uses regulated exocytosis of preterminal endocytic vesicles to transport cytosolic IL-1beta out of the cell. Indeed, although most of the IL-1beta precursor (proIL-1beta) localizes in the cytosol of activated human monocytes, a fraction is contained within vesicles that cofractionate with late endosomes and early lysosomes on Percoll density gradients and display ultrastructural features and markers typical of these organelles. The observation of organelles positive for both IL-1beta and the endolysosomal hydrolase cathepsin D or for both IL-1beta and the lysosomal marker Lamp-1 further suggests that they belong to the preterminal endocytic compartment. In addition, similarly to lysosomal hydrolases, secretion of IL-1beta is induced by acidotropic drugs. Treatment of monocytes with the sulfonylurea glibenclamide inhibits both IL-1beta secretion and vesicular accumulation, suggesting that this drug prevents the translocation of proIL-1beta from the cytosol into the vesicles. A high concentration of extracellular ATP and hypotonic medium increase secretion of IL-1beta but deplete the vesicular proIL-1beta content, indicating that exocytosis of proIL-1beta-containing vesicles is regulated by ATP and osmotic conditions.

MeSH Terms
Adenosine Triphosphate/metabolism Antigens, CD/metabolism Cells, Cultured Endopeptidases/drug effects,metabolism Exocytosis/physiology Extracellular Matrix/metabolism Glyburide/pharmacology Gold Humans Hydrogen-Ion Concentration Hypoglycemic Agents/pharmacology Interleukin-1/metabolism Lipopolysaccharides/pharmacology Lysosome-Associated Membrane Glycoproteins Membrane Glycoproteins/metabolism Monocytes/drug effects,metabolism Organelles/drug effects,metabolism,ultrastructure Osmotic Pressure Protein Precursors/drug effects,metabolism
Chemicals
Antigens, CD Hypoglycemic Agents Interleukin-1 Lipopolysaccharides Lysosome-Associated Membrane Glycoproteins Membrane Glycoproteins Protein Precursors Gold Adenosine Triphosphate Endopeptidases Glyburide
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Andrei C
National Cancer Institute, 16132 Genova, Italy.
Dazzi C
Lotti L
Torrisi M R
Chimini G
Rubartelli A
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.10.5.1463
Published
1999-05-00
Pages
1463-75
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC25302
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.10.5.1463 PMC Full Text View journal details
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