How botulinum and tetanus neurotoxins block neurotransmitter release

被引:304
作者
Humeau, Y
Doussau, F
Grant, NJ
Poulain, B
机构
[1] Ctr Neurochim, UPR 9009 CNRS, Lab Neurobiol Cellulaire, F-67084 Strasbourg, France
[2] Ctr Neurochim, INSERM U338, F-67084 Strasbourg, France
关键词
botulinum neurotoxins; tetanus toxin; Clostridium; quantal release; neurotransmission; membrane fusion; synaptic vesicle; SNARE complex; VAMP; synaptobrevin; SNAP-25; syntaxin;
D O I
10.1016/S0300-9084(00)00216-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Botulinum neurotoxins (BoNT, serotypes A-G) and tetanus neurotoxin (TeNT) are bacterial proteins that comprise a light chain (M-r approximate to 50) disulfide linked to a heavy chain (M-r approximate to 100). By inhibiting neurotransmitter release at distinct synapses, these toxins cause two severe neuroparalytic diseases, tetanus and botulism. The cellular and molecular modes of action of three toxins have almost been deciphered. After binding to specific membrane accepters, BoNTs and TeNT are internalized via endocytosis into nerve terminals. Subsequently, their light chain (a zinc-dependent endopeptidase) is translocated into the cytosolic compartment where it cleaves one of three essential proteins involved in the exocytotic machinery: Vesicle associated membrane protein (also termed synaptobrevin), syntaxin, and synaptosomal associated protein of 25 kDa. The aim of this review is to explain how the proteolytic attack at specific sites of the targets for BoNTs and TeNT induces perturbations of the fusogenic SNARE complex dynamics and how these alterations can account for the inhibition of spontaneous and evoked quantal neurotransmitter release by the neurotoxins. (C) 2000 Societe francaise de biochimie et biologie moleculaire / Editions scientifiques et medicales Elsevier SAS.
引用
收藏
页码:427 / 446
页数:20
相关论文
共 220 条
[1]   Effect of 3,4-diaminopyridine on rat extensor digitorum longus muscle paralyzed by local injection of botulinum neurotoxin [J].
Adler, M ;
Macdonald, DA ;
Sellin, LC ;
Parker, GW .
TOXICON, 1996, 34 (02) :237-249
[2]   Efficacy of a novel metalloprotease inhibitor on botulinum neurotoxin B activity [J].
Adler, M ;
Nicholson, JD ;
Hackley, BE .
FEBS LETTERS, 1998, 429 (03) :234-238
[3]   GT1B GANGLIOSIDE PREVENTS TETANUS TOXIN-INDUCED PROTEIN-KINASE-C ACTIVATION AND DOWN-REGULATION IN THE NEONATAL BRAIN INVIVO [J].
AGUILERA, J ;
PADROSGIRALT, C ;
HABIG, WH ;
YAVIN, E .
JOURNAL OF NEUROCHEMISTRY, 1993, 60 (02) :709-713
[4]   INVIVO TRANSLOCATION AND DOWN-REGULATION OF PROTEIN KINASE-C FOLLOWING INTRAVENTRICULAR ADMINISTRATION OF TETANUS TOXIN [J].
AGUILERA, J ;
YAVIN, E .
JOURNAL OF NEUROCHEMISTRY, 1990, 54 (01) :339-342
[5]   THE TETANUS TOXIN LIGHT CHAIN INHIBITS EXOCYTOSIS [J].
AHNERTHILGER, G ;
WELLER, U ;
DAUZENROTH, ME ;
HABERMANN, E ;
GRATZL, M .
FEBS LETTERS, 1989, 242 (02) :245-248
[6]   COMPARISON OF THE INTRACELLULAR EFFECTS OF CLOSTRIDIAL NEUROTOXINS ON EXOCYTOSIS FROM STREPTOLYSIN O-PERMEABILIZED RAT PHEOCHROMOCYTOMA (PC-12) AND BOVINE ADRENAL CHROMAFFIN CELLS [J].
AHNERTHILGER, G ;
WELLER, U .
NEUROSCIENCE, 1993, 53 (02) :547-552
[7]   Rho proteins: Targets for bacterial toxins [J].
Aktories, K .
TRENDS IN MICROBIOLOGY, 1997, 5 (07) :282-288
[8]  
ALEXANDER EA, 1997, AM J PHYSIOL, V272, P1054
[9]   Tetanus toxin inhibits neuroexocytosis even when its Zn2+-dependent protease activity is removed [J].
Ashton, AC ;
Li, Y ;
Doussau, F ;
Weller, U ;
Dougan, G ;
Poulain, B ;
Dolly, JO .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (52) :31386-31390
[10]  
Avery J, 1997, J CELL SCI, V110, P1555