Time course and temperature dependence of the membrane translocation of tetanus and botulinum neurotoxins C and D in neurons

Marco Pirazzini; Ornella Rossetto; Cristina Bertasio; Fulvio Bordin; Clifford Shone; Thomas Binz; Cesare Montecucco

doi:10.1016/j.bbrc.2012.11.048

Time course and temperature dependence of the membrane translocation of tetanus and botulinum neurotoxins C and D in neurons

Marco Pirazzini, Ornella Rossetto, Cristina Bertasio, Fulvio Bordin, Clifford Shone, Thomas Binz, Cesare Montecucco^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

28 Citations (Scopus)

Abstract

Tetanus and botulinum neurotoxins act inside nerve terminals and, therefore, they have to translocate across a membrane to reach their targets. This translocation is driven by a pH gradient, acidic on the cis side and neutral on the cytosol. Recently, a protocol to induce translocation from the plasma membrane was established. Here, we have used this approach to study the temperature dependence and time course of the entry of the L chain of tetanus neurotoxin and of botulinum neurotoxins type C and D across the plasma membrane of cerebellar granular neurons. The time course of translocation of the L chain varies for the three neurotoxins, but it remains in the range of minutes at 37°C, whilst it takes much longer at 20°C. BoNT/C does not enter neurons at 20°C. Translocation also depends on the dimension of the pH gradient. These data are discussed with respect to the contribution of the membrane translocation step to the total time to paralysis and to the low toxicity of these neurotoxins in cold-blood vertebrates.

Original language	English
Pages (from-to)	38-42
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	430
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2012.11.048
Publication status	Published - 4 Jan 2013

Bibliographical note

Funding Information:
The present work was supported by grants from: the Ministero dell’Università e della Ricerca (Progetto PRIN) and of the University of Padova to or, the Progetto Strategico and from Fondazione CARIPARO to CM, the HPA, NIHR Centre for Health Protection Research grant to CS , and the Deutsche Forschungsgemeinschaft (BI 660/3-1) to T.B .

Keywords

Botulinum neurotoxin
Botulism
Tetanus
Tetanus neurotoxin
Time course

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10.1016/j.bbrc.2012.11.048

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title = "Time course and temperature dependence of the membrane translocation of tetanus and botulinum neurotoxins C and D in neurons",

abstract = "Tetanus and botulinum neurotoxins act inside nerve terminals and, therefore, they have to translocate across a membrane to reach their targets. This translocation is driven by a pH gradient, acidic on the cis side and neutral on the cytosol. Recently, a protocol to induce translocation from the plasma membrane was established. Here, we have used this approach to study the temperature dependence and time course of the entry of the L chain of tetanus neurotoxin and of botulinum neurotoxins type C and D across the plasma membrane of cerebellar granular neurons. The time course of translocation of the L chain varies for the three neurotoxins, but it remains in the range of minutes at 37°C, whilst it takes much longer at 20°C. BoNT/C does not enter neurons at 20°C. Translocation also depends on the dimension of the pH gradient. These data are discussed with respect to the contribution of the membrane translocation step to the total time to paralysis and to the low toxicity of these neurotoxins in cold-blood vertebrates.",

keywords = "Botulinum neurotoxin, Botulism, Tetanus, Tetanus neurotoxin, Time course",

author = "Marco Pirazzini and Ornella Rossetto and Cristina Bertasio and Fulvio Bordin and Clifford Shone and Thomas Binz and Cesare Montecucco",

note = "Funding Information: The present work was supported by grants from: the Ministero dell{\textquoteright}Universit{\`a} e della Ricerca (Progetto PRIN) and of the University of Padova to or, the Progetto Strategico and from Fondazione CARIPARO to CM, the HPA, NIHR Centre for Health Protection Research grant to CS , and the Deutsche Forschungsgemeinschaft (BI 660/3-1) to T.B .",

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AU - Pirazzini, Marco

AU - Rossetto, Ornella

AU - Bertasio, Cristina

AU - Bordin, Fulvio

AU - Shone, Clifford

AU - Binz, Thomas

AU - Montecucco, Cesare

N1 - Funding Information: The present work was supported by grants from: the Ministero dell’Università e della Ricerca (Progetto PRIN) and of the University of Padova to or, the Progetto Strategico and from Fondazione CARIPARO to CM, the HPA, NIHR Centre for Health Protection Research grant to CS , and the Deutsche Forschungsgemeinschaft (BI 660/3-1) to T.B .

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N2 - Tetanus and botulinum neurotoxins act inside nerve terminals and, therefore, they have to translocate across a membrane to reach their targets. This translocation is driven by a pH gradient, acidic on the cis side and neutral on the cytosol. Recently, a protocol to induce translocation from the plasma membrane was established. Here, we have used this approach to study the temperature dependence and time course of the entry of the L chain of tetanus neurotoxin and of botulinum neurotoxins type C and D across the plasma membrane of cerebellar granular neurons. The time course of translocation of the L chain varies for the three neurotoxins, but it remains in the range of minutes at 37°C, whilst it takes much longer at 20°C. BoNT/C does not enter neurons at 20°C. Translocation also depends on the dimension of the pH gradient. These data are discussed with respect to the contribution of the membrane translocation step to the total time to paralysis and to the low toxicity of these neurotoxins in cold-blood vertebrates.

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KW - Botulinum neurotoxin

KW - Botulism

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KW - Tetanus neurotoxin

KW - Time course

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Time course and temperature dependence of the membrane translocation of tetanus and botulinum neurotoxins C and D in neurons

Abstract

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Keywords

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