An E3-ligase-based method for ablating inhibitory synapses

Garrett G. Gross

doi:10.1038/nmeth.3894

An E3-ligase-based method for ablating inhibitory synapses

2016-06-06

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DOI：10.1038/nmeth.3894

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Although neuronal activity can be modulated using a variety of techniques, there are currently few methods for controlling neuronal connectivity. We introduce a tool (GFE3) that mediates the fast, specific and reversible elimination of inhibitory synaptic inputs onto genetically determined neurons. GFE3 is a fusion between an E3 ligase, which mediates the ubiquitination and rapid degradation of proteins, and a recombinant, antibody-like protein (FingR) that binds to gephyrin. Expression of GFE3 leads to a strong and specific reduction of gephyrin in culture or in vivo and to a substantial decrease in phasic inhibition onto cells that express GFE3. By temporarily expressing GFE3 we showed that inhibitory synapses regrow following ablation. Thus, we have created a simple, reversible method for modulating inhibitory synaptic input onto genetically determined cells.

Keywords:

RECOMBINANT PROBES

SYNAPTIC PROTEINS

ZEBRAFISH

GEPHYRIN

NEURONS

GABA(A)

DOMAIN

DEGRADATION

MODULATION

STABILITY

An E3-ligase-based method for ablating inhibitory synapses

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