Botulinum neurotoxin A and neurotoxin E cleavage products of synaptosome-associated protein of 25 kd exhibit distinct actions on pancreatic islet beta-cell Kv2.1 channel gating

Pancreas
Yan HeHerbert Y Gaisano

Abstract

Synaptosome-associated protein of 25 kd (SNAP-25) regulates pancreatic islet beta-cell-delayed rectifier K channels (Kv2.1) in addition to insulin exocytosis. Botulinum neurotoxin A (BoNT/A) and E (BoNT/E) cleavage and presumed deletion of SNAP-25 have been used to examine SNAP-25 function. We hypothesized that proteolytic products of SNAP-25 (206 amino acids) resulting from BoNT/A and BoNT/E cleavage, SNAP-25(1-197) and SNAP-25(1-180), have independent actions on beta-cell Kv gating. We examined by confocal microscopy and immunoblotting BoNT/A and BoNT/E cleavage of SNAP-25 to these N-terminal fragments, and the consequent effects of these BoNTs and SNAP-25 fragments on Kv currents in rat beta cells and MIN6 cells by patch clamp electrophysiology. Confocal microscopy and immunoblotting showed that MIN6 cells transfected with BoNT/A or BoNT/E generated SNAP-25(1-197) and SNAP-25(1-180) fragments that were retained in the cytosol. Both BoNTs caused increased rate of channel activation and slowed channel inactivation, mimicked by these SNAP-25 fragments, but not full-length SNAP-25. These SNAP-25 fragments potentiated tetraethylammonium block of beta-cell Kv currents. BoNT/A or BoNT/E treatment of beta cells generates N-terminal ...Continue Reading

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Citations

Jan 1, 2014·Neuroscience Letters·Saori YamamoriMasami Takahashi
Jun 11, 2014·Progress in Neurobiology·Ivica Matak, Zdravko Lacković
Oct 27, 2009·Toxicon : Official Journal of the International Society on Toxinology·Chueh-Ling KuoCharles B Shoemaker
Dec 24, 2008·Biochemical and Biophysical Research Communications·Guo-qing ZhuangYan He
Feb 1, 2011·The Journal of Comparative Neurology·Saori YamamoriMasami Takahashi
May 14, 2014·British Journal of Pharmacology·Roshni Ramachandran, Tony L Yaksh
May 29, 2015·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·P BarbantiS Piroso

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Botulism is a rare but serious paralytic illness caused by a nerve toxin that is produced by the bacterium clostridium botulinum. Discover the latest research on botulism here.

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Botulism is a rare but serious paralytic illness caused by a nerve toxin that is produced by the bacterium clostridium botulinum. Discover the latest research on botulism here.