BoTox toxin turned into a precision research tool
January 2019. Regulated secretion is critical for diverse biological processes ranging from immune and endocrine signaling to synaptic transmission. Botulinum and tetanus neurotoxins, which specifically destroy vesicle fusion proteins involved in regulated secretion, have been widely used as experimental tools to block these processes. Genetic expression of these toxins in the nervous system has been a powerful research approach for disrupting neurotransmitter release within defined circuitry, but their current utility in brain research and elsewhere remains limited by lack of spatial and temporal control.
A team of scientists from the University of Colorado School of Medicine and Goethe University Frankfurt now managed to engineer botulinum neurotoxin B so that it can be activated with blue light. The scientists demonstrated the utility of this approach for inducibly disrupting excitatory neurotransmission in the lab, providing a first-in-class optogenetic tool for persistent, light-triggered synaptic inhibition.
In addition to blocking neurotransmitter release, this approach will have broad utility in research for conditionally disrupting regulated secretion of diverse bioactive molecules, including neuropeptides, neuromodulators, hormones and immune molecules.
Liu Q, Sinnen BL, Boxer EE, Schneider MW, Grybko MJ, Buchta WC, Gibson ES, Wysoczynski CL, Ford CP, Gottschalk A, Aoto J, Tucker CL, Kennedy MJ (2019) A photoactivatable botulinum neurotoxin for inducible control of neurotransmission. Neuron: published online 28 January 2019. doi 10.1016/j.neuron.2019.01.002
Alexander Gottschalk, Buchmann Institute for Molecular Life Sciences and Institute of Biophysical Chemistry, Riedberg Campus, Goethe University, Frankfurt/Main, Germany, a.gottschalk(at)em.uni-frankfurt.de.