TI-VAMP/VAMP7 is the SNARE of secretory lysosomes contributing to ATP secretion from astrocytes

Claudia Verderio, Cinzia Cagnoli, Matteo Bergami, Maura Francolini, Ursula Schenk, Alessio Colombo, Loredana Riganti, Carolina Frassoni, Emanuela Zuccaro, Lydia Danglot, Claire Wilhelm, Thierry Galli, Marco Canossa, Michela Matteoli

Research output: Contribution to journalArticlepeer-review


Background information: ATP is the main transmitter stored and released from astrocytes under physiological and pathological conditions. Morphological and functional evidence suggest that besides secretory granules, secretory lysosomes release ATP. However, the molecular mechanisms involved in astrocytic lysosome fusion remain still unknown. Results: In the present study, we identify tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP, also called VAMP7) as the vesicular SNARE which mediates secretory lysosome exocytosis, contributing to release of both ATP and cathepsin B from glial cells. We also demonstrate that fusion of secretory lysosomes is triggered by slow and locally restricted calcium elevations, distinct from calcium spikes which induce the fusion of glutamate-containing clear vesicles. Downregulation of TI-VAMP/VAMP7 expression inhibited the fusion of ATP-storing vesicles and ATP-mediated calcium wave propagation. TI-VAMP/VAMP7 downregulation also significantly reduced secretion of cathepsin B from glioma. Conclusions: Given that sustained ATP release from glia upon injury greatly contributes to secondary brain damage and cathepsin B plays a critical role in glioma dissemination, TI-VAMP silencing can represent a novel strategy to control lysosome fusion in pathological conditions.

Original languageEnglish
Pages (from-to)213-228
Number of pages16
JournalBiology of the cell / under the auspices of the European Cell Biology Organization
Issue number4
Publication statusPublished - Apr 2012


  • Astrocytes
  • ATP
  • Cathepsin B
  • Secretory lysosomes

ASJC Scopus subject areas

  • Cell Biology


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