The small chemical vacuolin-1 inhibits Ca(2+)-dependent lysosomal exocytosis but not cell resealing.
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 Ca(2+)-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.
Department of Cell Biology and The CBR Institute for Biomedical Research, Harvard Medical School, Boston, Massachusetts 02115, USA.
Jan
J
Cerny
Yan
Y
Feng
Anan
A
Yu
Katsuya
K
Miyake
Barbara
B
Borgonovo
Judith
J
Klumperman
Jacopo
J
Meldolesi
Paul L
PL
McNeil
Tomas
T
Kirchhausen
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D011992:Endosomes / Q000648:ultrastructure; D005089:Exocytosis / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006576:Heterocyclic Compounds, 4 or More Rings; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron
D003598:Cytoskeletal Proteins; D006576:Heterocyclic Compounds, 4 or More Rings; D007476:Ionophores; C503870:vacuolin-1; D015759:Ionomycin; D002118:Calcium