Cleavage of cellubrevin by tetanus toxin does not affect fusion of early endosomes.
Tetanus toxin is a potent inhibitor of neurotransmitter release, which acts as an intracellular metalloendoprotease that selectively cleaves synaptobrevin, a major membrane protein of synaptic vesicles. Recently, synaptobrevin has been found to form an ATP-dependent complex with N-ethylmaleimide-sensitive fusion protein (NSF) and soluble NSF attachment protein, which are known to function in endosome fusion. Furthermore, a highly homologous isoform of synaptobrevin, named cellubrevin, was identified that is expressed in virtually all tissues in the endocytic pathway and is cleaved by tetanus toxin light chain in vitro, suggesting that cellubrevin may have a general function in intracellular fusion events. In the present study, we have analyzed whether cleavage of cellubrevin by tetanus toxin influences the ATP-dependent, N-ethylmaleimide-sensitive fusion of early endosomes in vitro. Our results show that endosome fusion is not affected by tetanus toxin although cellubrevin is almost completely proteolyzed, suggesting that the function of NSF in endosome fusion does not involve cellubrevin.
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Department of Pharmacology, Yale University Medical School, New Haven, Connecticut 06510.
McMahon
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Fischer von Mollard
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Yamasaki
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Niemann
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Südhof
T C
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Jahn
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D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D004705:Endocytosis; D005033:Ethylmaleimide / Q000494:pharmacology; D007425:Intracellular Membranes / Q000502:physiology*; D007668:Kidney; D007700:Kinetics; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000378:metabolism*; D052066:N-Ethylmaleimide-Sensitive Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism; D015388:Organelles / Q000648:ultrastructure; D050683:R-SNARE Proteins; D013744:Tetanus Toxin / Q000378:metabolism*; D051040:Vesicle-Associated Membrane Protein 3; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050683:R-SNARE Proteins; D013744:Tetanus Toxin; D051040:Vesicle-Associated Membrane Protein 3; D033921:Vesicular Transport Proteins; D000255:Adenosine Triphosphate; D052066:N-Ethylmaleimide-Sensitive Proteins; D005033:Ethylmaleimide