News tips from the Journal of Neuroscience

1. Targeting of Calcium Channels to Active Zones
A. Ashleigh Long, Eunju Kim, Hung-Tat Leung, Elvin Woodruff III, Lingling An, R. W. Doerge, William L. Pak, and Kendal Broadie

This week, Long et al. describe a newly discovered Drosophila protein, fuseless, that is required for vesicle fusion. Fuseless is a transmembrane protein expressed in presynaptic membranes in retina and neuromuscular junctions. Synaptic transmission was impaired in fuseless mutants but was rescued by expression of the transgene exclusively in presynaptic cells. Although synapses appeared essentially normal in mutants, the number of synaptic vesicles was nearly double that in wild-type flies, indicating impairment of exocytosis. The amplitude of evoked excitatory junction potentials was greatly reduced in mutants, and raising extracellular calcium concentration increased the amplitude much less in mutants than in controls, suggesting that a defect in calcium entry underlies the defect in vesicle fusion. Indeed, the expression pattern of voltage-sensitive calcium channels (VSCCs) was disrupted in mutants—the channels were no longer clustered in active zones. Thus, Fuseless is necessary for proper targeting of VSCCs, which enables the localized calcium influx necessary for vesicle release.

2. Could Botulinum Toxin Be Bad for You?
Flavia Antonucci, Chiara Rossi, Laura Gianfranceschi, Ornella Rossetto, and Matteo Caleo

Botulinum toxins (BoNTs) are used increasingly to treat maladies from spasms and migraines to obesity and wrinkles. It has been assumed that the toxin remains localized at the injection site, where it cleaves proteins involved in vesicle fusion, thereby blocking neurotransmitter release. But now Antonucci et al. demonstrate that BoNT/A is retrogradely transported along microtubules, transcytosed, and taken up by afferent terminals. When BoNT/A was injected into one hippocampus in rats, it cleaved its target [synaptosomal-associated protein of 25 kDa (SNAP-25)] in the contralateral hippocampus, resulting in reduced neuronal activity. Similarly, when BoNT/A was injected into the superior colliculus or whisker pads, SNAP-25 was cleaved in the retina and facial nucleus, respectively. In the retina, BoNT/A remained active for at least 25 d after injection. Although cleaved SNAP-25 was detected only in afferents that projected directly to the injection site, it is not clear whether further transcytosis would occur over time.