Application of the SNARE Hypothesis to Insulin Exocytosis

The t-SNARE SNAP-25 is also expressed in the P-cell and has been localized mainly to the plasma membrane (Sadoul etal., 1995). SNAP-25 was cleaved by treatment of SLO-permeabilized cells with botulinum toxins (BoNT) A or E. The two neurotoxins inhibited Ca -induced insulin exocytosis but failed to abolish the process completely (Sadoul ef al., 1995). This could be due to the failure of the toxins to cleave SNAP-25 already complexed to other fusion proteins (escaping detection by Western blotting) or to the requirement for SNAP-25 at a penultimate step in insulin exocytosis. 

The other t-SNARE candidate protein, syntaxin, is also expressed in islet cells (Jacobsson ef al., 1994). Treatment of digitonin- 

Clostridial Toxins and Endocrine Secretion Their Use in Insulin-Secreting Cells 221 

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