Transient expression of botulinum neurotoxin C1 light chain differentially inhibits calcium and glucose induced insulin secretion in clonal β‐cells

FEBS Letters

Wollheim, Claes B¹  Zhang, Hui¹  Vaidyanathan, Vadakkanchery-Viswanathan³  Sadoul, Karin²  Niemann, Heiner³  Lang, Jochen¹ 

[1] Division de Biochimie Clinique, Département de Médecine Interne, Centre Médical Universitaire, 1 rue Michel Servet, Université de Genève, CH-1211 Geneva 4, Switzerland;Laboratoires de Recherche Louis Jeantet, Centre Médical Universitaire, Université de Genève, Geneva, Switzerland;Institut für Biochemie, Medizinische Hochschule, Hannover, Germany

关键词: Exocytosis;    Ca2+;    Guanosine triphosphate;    Glucose;    Botulinum neurotoxin C1;    Insulin;    α/β-SNAP;    soluble NSF attachment proteins;    BoNT;    botulinum neurotoxin;    BoNT C1;    botulinum neurotoxin C1;    BoNT E;    botulinum neurotoxin E;    eGFP/BoNT C1;    enhanced GFP-botulinum neurotoxin C1 fusion protein;    NSF;    N-ethylmaleimide sensitive factor;    phINS;    plasmid encoding human insulin;    SNARE;    soluble NSF attachment receptor;    VAMP;    vesicle associated membrane protein;   

DOI  :  10.1016/S0014-5793(97)01411-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We have investigated the effect of botulinum neurotoxin (BoNT) C1 light chain (LC) on insulin exocytosis from the clonal β-cell line HIT-T15. In streptolysin-O permeabilized cells, the β-cell impermeant BoNT C1 cleaved mainly syntaxin 1 and inhibited Ca²⁺ as well as GTPγS induced exocytosis. To study the effect of BoNTs in intact cells, we transiently coexpressed the BoNT LC together with a reporter gene for insulin release. BoNT C1 inhibited K⁺ induced insulin secretion by 95% but reduced insulin release stimulated by glucose only by 25%. Thus a component of glucose stimulated insulin release is insensitive to BoNT C1.

【 授权许可】

Unknown