BOTULINUM-A AND THE LIGHT-CHAIN OF TETANUS TOXINS INHIBIT DISTINCT STAGES OF MG-CENTER-DOT-ATP-DEPENDENT CATECHOLAMINE EXOCYTOSIS FROM PERMEABILIZED CHROMAFFIN CELLS

被引:61
作者
LAWRENCE, GW
WELLER, U
DOLLY, JO
机构
[1] UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,DEPT BIOCHEM,LONDON SW7 2AY,ENGLAND
[2] UNIV MAINZ,INST MED MIKROBIOL,FACHBEREICH MED,MAINZ,GERMANY
来源
EUROPEAN JOURNAL OF BIOCHEMISTRY | 1994年 / 222卷 / 02期
关键词
D O I
10.1111/j.1432-1033.1994.tb18871.x
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
Susceptibilities of Mg . ATP-independent and Mg . ATP-requiring components of catecholamine secretion from digitonin-permeabilised chromaffin cells to inhibition by Clostridial botulinum type A and tetanus toxins were investigated. These toxins are Zn2+-dependent proteases which specifically cleave the 25-kDa synaptosomal-associated protein (SNAP-25) and vesicle-associated membrane protein (VAMP) II, respectively. When applied to permeabilised chromaffin cells they rapidly inhibited secretion in the presence of Mg . ATP but the catecholamine released in the absence of Mg . ATP, thought to represent fusion of primed granules, was not perturbed. The toxins, can exert their effects per se in the absence of the nucleotide complex; therefore, Mg . ATP-requiring steps of secretion are implicated as roles for their targets. Primed release was lost rapidly after permeabilisation of the cells but could be maintained by including Mg . ATP during the incubation before stimulating release with Ca2+. This ability of Mg . ATP to maintain primed release was only partially inhibited by botulinum neurotoxin A whereas it was abolished by tetanus toxin, consistent with the distinct substrates for these toxins. This study reveals a component of release within which these proteins are either resistant to cleavage by these toxins or in such a position that degradation can no longer prevent granule fusion. Differences in the steps of release at which these toxins can affect inhibition are also revealed.
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页码:325 / 333
页数:9
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