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The small chemical vacuolin‐1 inhibits Ca2+‐dependent lysosomal exocytosis but not cell resealing

Jan Cerny, Yan Feng, Anan Yu, Katsuya Miyake, Barbara Borgonovo, Judith Klumperman, Jacopo Meldolesi, Paul L McNeil, Tomas Kirchhausen

Author Affiliations

  1. Jan Cerny1,2,
  2. Yan Feng3,
  3. Anan Yu1,
  4. Katsuya Miyake4,
  5. Barbara Borgonovo5,
  6. Judith Klumperman6,
  7. Jacopo Meldolesi5,
  8. Paul L McNeil4 and
  9. Tomas Kirchhausen*,1,3
  1. 1 Department of Cell Biology and The CBR Institute for Biomedical Research, Harvard Medical School, Boston, Massachusetts, 02115, USA
  2. 2 Department of Physiology of Animals and Developmental Biology, Charles University, Prague 2, Czech Republic
  3. 3 Institute of Chemistry and Cell Biology, ICCB, Harvard Medical School, Boston, Massachusetts, 02115, USA
  4. 4 Department of Cellular Biology and Anatomy and Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia, 30912, USA
  5. 5 Department of Neuroscience, DIBIT, Vita‐Salute San Raffaele University and San Raffaele Institute, Via Olgettina 58, 20132, Milano, Italy
  6. 6 Department of Cell Biology, University Medical Centre and Institute for Biomembranes, Heidelberglaan 100, 3584, Utrecht, The Netherlands
  1. *Corresponding author. Tel: +1 617 278 3140; Fax: +1 617 278 3131; E-mail: kirchhausen{at}crystal.harvard.edu
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Abstract

Resealing after wounding, the process of repair following plasma membrane damage, requires exocytosis. Vacuolins are molecules that induce rapid formation of large, swollen structures derived from endosomes and lysosomes by homotypic fusion combined with uncontrolled fusion of the inner and limiting membranes of these organelles. Vacuolin‐1, the most potent compound, blocks the Ca2+‐dependent exocytosis of lysosomes induced by ionomycin or plasma membrane wounding, without affecting the process of resealing. In contrast, other cell structures and membrane trafficking functions including exocytosis of enlargeosomes are unaffected. Because cells heal normally in the presence of vacuolin‐1, we suggest that lysosomes are dispensable for resealing.

  • Received May 14, 2004.
  • Revision received July 9, 2004.
  • Accepted July 29, 2004.
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