Truncated SNAP-25 (1-197), like botulinum neurotoxin A, can inhibit insulin secretion from HIT-T15 insulinoma cells

Molecular Endocrinology
X HuangH Y Gaisano

Abstract

We and others have previously shown that insulin-secreting cells of the pancreas express high levels of SNAP-25 (synaptosomal-associated protein of 25 kDa), a 206-amino acid t-SNARE (target soluble N-ethylmaleimide-sensitive factor attachment protein receptors) implicated in synaptic vesicle exocytosis. In the present study, we show that SNAP-25 is required for insulin secretion by transient transfection of Botulinum Neurotoxin A (BoNT/A) into insulin-secreting HIT-T15 cells. Transient expression of BoNT/A cleaved the endogenous as well as overexpressed SNAP-25 proteins and caused significant reductions in K+ and glucose-evoked secretion of insulin. To determine whether the inhibition of release was due to the depletion of functional SNAP-25 or the accumulation of proteolytic by-products, we transfected cells with SNAP-25 proteins from which the C-terminal nine amino acids had been deleted to mimic the effects of the toxin. This modified SNAP-25 (amino acids 1-197) remained bound to the plasma membrane but was as effective as the toxin at inhibiting insulin secretion. Microfluorimetry revealed that the inhibition of secretion was due neither to changes in basal cytosolic Ca2+ levels nor in Ca2+ influx evoked by K(+)-mediated pl...Continue Reading

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Citations

Dec 28, 2012·American Journal of Physiology. Renal Physiology·Mariela Mendez, Herbert Y Gaisano
Jun 12, 2013·Cellular and Molecular Life Sciences : CMLS·Sergio Pantano, Cesare Montecucco
Jun 11, 2009·American Journal of Physiology. Endocrinology and Metabolism·Jenny VikmanLena Eliasson
Jan 18, 2020·Toxins·Shivam Om Mittal, Bahman Jabbari
Aug 8, 2019·Toxins·Ivica MatakZsuzsanna Helyes
Apr 30, 2002·Diabetes·Junzhi JiHerbert Y Gaisano
Dec 25, 2021·Applied Microbiology and Biotechnology·Tomasz GrendaKrzysztof Kwiatek

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