VAMP/synaptobrevin cleavage by tetanus and botulinum neurotoxins is strongly enhanced by acidic liposomes

FEBS Letters

Montecucco, Cesare³  Rigoni, Michela³  Rossetto, Ornella³  Johnson, Eric¹  Schiavo, Giampietro²  Caccin, Paola³ 

[1] Department of Food Microbiology and Toxicology, University of Wisconsin, Madison, WI, USA;Laboratory of Neuropathobiology, Cancer Research UK, London Research Institute, Lincoln's Inn Fields laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK;Istituto di Neuroscienze del CNR Biomembrane and Dipartimento di Scienze Biomediche, Università di Padova, Via G. Colombo 3, 35121 Padova, Italy

关键词: Tetanus neurotoxin;    Botulinum neurotoxin;    Vesicle associated membrane protein/synaptobrevin;    Liposome;    BoNT;    botulinum neurotoxin;    LSB;    Laemmli sample buffer;    PBS;    phosphate-buffered saline;    SSV;    small synaptic vesicles;    TeNT;    tetanus neurotoxin;    VAMP;    vesicle associated membrane protein;   

DOI  :  10.1016/S0014-5793(03)00365-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Tetanus and botulinum neurotoxins (TeNT and BoNTs) block neuroexocytosis via specific cleavage and inactivation of SNARE proteins. Such activity is exerted by the N-terminal 50 kDa light chain (L) domain, which is a zinc-dependent endopeptidase. TeNT, BoNT/B, /D, /F and /G cleave vesicle associated membrane protein (VAMP), a protein of the neurotransmitter-containing small synaptic vesicles, at different single peptide bonds. Since the proteolytic activity of these metalloproteases is higher on native VAMP inserted in synaptic vesicles than on recombinant VAMP, we have investigated the influence of liposomes of different lipid composition on this activity. We found that the rate of VAMP cleavage with all neurotoxins tested here is strongly enhanced by negatively charged lipid mixtures. This effect is at least partially due to the binding of the metalloprotease to the lipid membranes, with electrostatic interactions playing an important role.

【 授权许可】

Unknown