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 in neurons and endocrine cells. It has been shown to play an important role in the release mechanism of neurotransmitters and peptide hormones, including insulin. Thus, when insulin-secreting cells are permeabilized and treated with botulinum neurotoxin E (BoNT/E), SNAP-25 is hydrolyzed, and insulin secretion is inhibited. Recently SNAP-23, a more generally expressed isoform of SNAP-25, has been described. The functional 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 possible to test whether transfection of HIT (transformed pancreatic B-) cells with SNAP-23 reconstitutes insulin release from BoNT/E treated cells, in which SNAP-25 is inactivated by the toxin. The results show that SNAP-23 is able to replace SNAP-25 when it is overexpressed. While these results demonstrate that SNAP-23 is a functional homologue of SNAP-25, able to function in regulated exocytosis, they indicate that SNAP-23 may be inefficient in this process. This suggests that both isoforms may have their own specific binding partners and discrete, albeit mechanistically similar, functional roles within the cell.
Sadoul
K
K
Laboratoires de Recherche Louis Jeantet, Centre Médical Universitaire, 1 rue Michel Servet, 1211 Geneva 4, Switzerland. karin.sadoul@medecine.unige.ch
Berger
A
A
Niemann
H
H
Weller
U
U
Roche
P A
PA
Klip
A
A
Trimble
W S
WS
Regazzi
R
R
Catsicas
S
S
Halban
P A
PA
D000818:Animals; D001905:Botulinum Toxins / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D019084:Fluorescent Antibody Technique, Indirect; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; D050825:Synaptosomal-Associated Protein 25; D014162:Transfection; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D007328:Insulin; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; C100493:SNAP23 protein, human; D050825:Synaptosomal-Associated Protein 25; D001905:Botulinum Toxins; C096326:botulinum toxin type E