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Common and distinct fusion proteins in axonal growth and transmitter release
Author(s) -
OsenSand Astrid,
Staple Julie K.,
Naldi Ezio,
Schiavo Giampietro,
Rossetto Ornella,
Petitpierre Sylvie,
Malgaroli Antonio,
Montecucco Cesare,
Catsicas Stefan
Publication year - 1996
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/(sici)1096-9861(19960401)367:2<222::aid-cne5>3.0.co;2-7
Subject(s) - biology , neuroscience
We have used the proteolytic properties of botulinum and tetanus neurotoxins (BoNT, TeNT) to cleave three proteins of the membrane fusion machinery, SNAP‐25, VAMP/synaptobrevin, and syntaxin, in developing and differentiated rat central neurons in vitro. Then, we have studied the capacity of neurons to extend neurites, make synapses, and release neurotransmitters. All the toxins showed the expected specificity with the exception that BoNT/C cleaved SNAP‐25 in addition to syntaxin and induced rapid neuronal death. In developing neurons, cleavage of SNAP‐25 with BoNT/A inhibited axonal growth and prevented synapse formation. In contrast, cleavage of VAMP with TeNT or BoNT/B had no effects on neurite extension and synaptogenesis. All the toxins tested inhibited transmitter release in differentiated neurons, and cleavage of VAMP resulted in the strongest inhibition. These data indicate that SNAP‐25 is involved in vesicle fusion for membrane expansion and transmitter release, whereas VAMP is selectively involved in transmitter release. In addition, our results support the hypothesis that synaptic activity is not essential for synapse formation in vitro. © 1996 Wiley‐Liss, Inc.