biostudies-literatureLiu QNEI NIH HHSDeutsche ForschungsgemeinschaftNIDA NIH HHSBrain Research FoundationNIMH NIH HHSNINDS NIH HHSNIHNIGMS NIH HHS863-875.e6https://www.ebi.ac.uk/biostudies/studies/S-EPMC6524650biostudies-literatureUnknown101(5)Regulated secretion is critical for diverse biological processes ranging from immune and endocrine signaling to synaptic transmission. Botulinum and tetanus neurotoxins, which specifically proteolyze 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 approach for disrupting neurotransmitter release within defined circuitry, but their current utility in the brain and elsewhere remains limited by lack of spatial and temporal control. Here we engineered botulinum neurotoxin B so that it can be activated with blue light. We demonstrate the utility of this approach for inducibly disrupting excitatory neurotransmission, 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 for conditionally disrupting regulated secretion of diverse bioactive molecules, including neuropeptides, neuromodulators, hormones, and immune molecules. VIDEO ABSTRACT.NeuronA Photoactivatable Botulinum Neurotoxin for Inducible Control of Neurotransmission.PMC6524650R01 GM100225GO1011/12-1R01NS1075541UF1NS107710CRC1080-B2R01DA35821R01 NS095809T32 GM007635R01NS082271R01 NS082271R01 NS107554R21EY026363SPP1926 – Next Generation OptogeneticsR21 EY026363R01NS95809R01 DA035821R01GM100225R00 MH103531R00MH103531UF1 NS107710Ford CPGrybko MJBoxer EESinnen BLSchneider MWLiu QAoto JTucker CLWysoczynski CLGibson ESGottschalk ABuchta WCKennedy MJfalseA Photoactivatable Botulinum Neurotoxin for Inducible Control of Neurotransmission.Regulated secretion is critical for diverse biological processes ranging from immune and endocrine signaling to synaptic transmission. Botulinum and tetanus neurotoxins, which specifically proteolyze 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 approach for disrupting neurotransmitter release within defined circuitry, but their current utility in the brain and elsewhere remains limited by lack of spatial and temporal control. Here we engineered botulinum neurotoxin B so that it can be activated with blue light. We demonstrate the utility of this approach for inducibly disrupting excitatory neurotransmission, 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 for conditionally disrupting regulated secretion of diverse bioactive molecules, including neuropeptides, neuromodulators, hormones, and immune molecules. VIDEO ABSTRACT.2019-01-01T00:00:00Z2019 Mar2024-11-20T23:55:19.16Z2020-10-29T12:17:30ZS-EPMC65246503070491110.1016/j.neuron.2019.01.002