Neuronal SNARE proteins are key players during the fusion of neurotransmitter containing vesicles with the plasma membrane. In Drosophila, expression of the tetanus neurotoxin light chain (TNT), which specifically cleaves neuronal synaptobrevin, leads to severe impairment of Ca²⁺ triggered transmitter release in neurons and has been successfully used to interfere with Drosophila behavior (Sweeney et al., 1995; Neuser et al. 2008). However, Drosophila photoreceptor function appears to be resistant to TNT expression (Rister and Heisenberg, 2006). A recent study demonstrates that botulinum-neurotoxin mediated cleavage of different SNARE proteins does not effect exocytosis in mouse inner ear hair cells (Nouvian et al., 2011). Taking into account the functional similarities of Drosophila photoreceptors and mouse inner ear hair cells, resistance to clostridial neurotoxins might reflect a common molecular specialization in order to meet the demands of tonic synaptic transmission. Thus we created several genetically encoded botulinum toxin light chains (BoNTs) that cleave different neuronal SNARE proteins for use in Drosophila. To confirm proteolysis of the different neuronal SNARE isoforms we performed biochemical assays in cell cultures and verified the effect of BoNT expression on larval neuromuscular junctions. Tests on the influence of BoNT expression on photoreceptor function are underway.

Neuser K, Triphan T, Mronz M, Poeck B, Strauss R (2008) Analysis of a spatial orientation memory in Drosophila. Nature 453:1244-1247.

Nouvian R, Neef J, Bulankina AV, Reisinger E, Pangršic T, Frank T, Sikorra S, Brose N, Binz T, Moser T (2011) Exocytosis at the hair cell ribbon synapse apparently operates without neuronal SNARE proteins. Nature Neuroscience 14:411-413.

Rister J, Heisenberg M (2006) Distinct functions of neuronal synaptobrevin in developing and mature fly photoreceptors. J Neurobiol. 12:1271-84.

Sweeney ST, Broadie K, Keane J, Neimann H, O’Kane CJ (1995) Targeted expression of tetanus toxin light chain in Drosophila specifically eliminates synaptic transmission and causes behavioral defects. Neuron 14:341-351.