SNAP-23 IS NOT CLEAVED BY BOTULINUM NEUROTOXIN-E AND CAN REPLACE SNAP-25 IN THE PROCESS OF INSULIN-SECRETION

The synaptosomal-associated protein of 25 kDa (SNAP-25) is expressed i n neurons and endocrine cells. It has been shown to play an important role in the release mechanism of neurotransmitters and peptide hormone s, including insulin. Thus, when insulin-secreting cells are permeabil ized and treated with botulinum neurotoxin E (BoNT/E), SNAP-25 is hydr olyzed, and insulin secretion is inhibited. Recently SNAP-23, a more g enerally expressed isoform of SNAP-25, has been described. The functio nal role of SNAP-23 has not been investigated to date. It is now shown that SNAP-23 is resistant to cleavage by BoNT/E. It was therefore pos sible to test whether transfection of HIT (transformed pancreatic B-) cells with SNAP-23 reconstitutes insulin release from BoNT/E treated c ells, in which SNAP-25 is inactivated by the toxin. The results show t hat SNAP-23 is able to replace SNAP-25 when it is overexpressed. While these results demonstrate that SNAP-23 is a functional homologue of S NAP-25, able to function in regulated exocytosis, they indicate that S NAP-23 may be inefficient in this process. This suggests that both iso forms may have their own specific binding partners and discrete, albei t mechanistically similar, functional roles within the cell.