A Photoactivatable Botulinum Neurotoxin for Inducible Control of Neurotransmission.

Autor:	Liu Q; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA., Sinnen BL; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA., Boxer EE; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA., Schneider MW; Buchmann Institute for Molecular Life Sciences and Institute of Biophysical Chemistry, Goethe University, Max-von-Laue-Strasse 15, 60438 Frankfurt, Germany., Grybko MJ; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA., Buchta WC; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA., Gibson ES; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA., Wysoczynski CL; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA., Ford CP; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA., Gottschalk A; Buchmann Institute for Molecular Life Sciences and Institute of Biophysical Chemistry, Goethe University, Max-von-Laue-Strasse 15, 60438 Frankfurt, Germany., Aoto J; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA., Tucker CL; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA. Electronic address: chandra.tucker@ucdenver.edu., Kennedy MJ; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA. Electronic address: matthew.kennedy@ucdenver.edu.
Jazyk:	angličtina
Zdroj:	Neuron [Neuron] 2019 Mar 06; Vol. 101 (5), pp. 863-875.e6. Date of Electronic Publication: 2019 Jan 28.
DOI:	10.1016/j.neuron.2019.01.002
Abstrakt:	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. (Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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