Endobrevin/VAMP8 mediates exocytotic release of hexosaminidase from rat basophilic leukaemia cells.
Mast cells are important players in innate immunity and mediate allergic responses. Upon stimulation, they release biologically active mediators including histamine, cytokines and lysosomal hydrolases. We used permeabilized rat basophilic leukaemia cells as model to identify R-SNAREs (soluble NSF (N-ethylmaleimide-sensitive fusion protein)) mediating exocytosis of hexosaminidase from mast cells. Of a complete set of recombinant mammalian R-SNAREs, only vesicle associated membrane protein (VAMP8)/endobrevin consistently blocked hexosaminidase release, which was also insensitive to treatment with clostridial neurotoxins. Thus, VAMP8, which also mediates fusion of late endosomes and lysosomes, plays a major role in hexosaminidase release, strengthening the view that mast cell granules share properties of both secretory granules and lysosomes.
Lippert
Undine
U
Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
Ferrari
David M
DM
Jahn
Reinhard
R
D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology; D001491:Basophils / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects; D005089:Exocytosis / Q000187:drug effects; D006596:Hexosaminidases / Q000378:metabolism*; D007938:Leukemia / Q000235:genetics / Q000378:metabolism*; D050683:R-SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D013301:Streptolysins / Q000494:pharmacology; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism; D051040:Vesicle-Associated Membrane Protein 3 / Q000378:metabolism
D001426:Bacterial Proteins; D050683:R-SNARE Proteins; D013301:Streptolysins; C491830:Vamp8 protein, rat; D050988:Vesicle-Associated Membrane Protein 2; D051040:Vesicle-Associated Membrane Protein 3; C025964:streptolysin O; D006596:Hexosaminidases; D002118:Calcium