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

Cristina Andrei, Cecilia Dazzi, Lavinia Lotti, Maria Rosaria Torrisi, Giovanna Chimini, Anna Rubartelli

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Interleukin 1β (IL-1β), 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-1β out of the cell. Indeed, although most of the IL-1β precursor (proIL-1β) 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-1β and the endolysosomal hydrolase cathepsin D or for both IL-1β 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-1β is induced by acidotropic drugs. Treatment of monocytes with the sulfonylurea glibenclamide inhibits both IL-1β secretion and vesicular accumulation, suggesting that this drug prevents the translocation of proIL-1β from the cytosol into the vesicles. A high concentration of extracellular ATP and hypotonic medium increase secretion of IL-1β but deplete the vesicular proIL-1β content, indicating that exocytosis of proIL-1β-containing vesicles is regulated by ATP and osmotic conditions.

Original languageEnglish
Pages (from-to)1463-1475
Number of pages13
JournalMolecular Biology of the Cell
Issue number5
Publication statusPublished - May 1999

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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