Affiliated with Université Laval & CERVO Research Centre

An E3-ligase-based method for ablating inhibitory synapses.

TitleAn E3-ligase-based method for ablating inhibitory synapses.
Publication TypeJournal Article
Year of Publication2016
AuthorsGross GG, Straub C, Perez-Sanchez J, Dempsey WP, Junge JA, Roberts RW, Trinh LA, Fraser SE, De Koninck Y, De Koninck P, Sabatini BL, Arnold DB
JournalNat Methods
Date Published2016 Aug
KeywordsAnimals, Carrier Proteins, Cells, Cultured, Embryo, Mammalian, Female, Hippocampus, Male, Membrane Proteins, Motor Disorders, Neurons, Patch-Clamp Techniques, Rats, Rats, Sprague-Dawley, Spine, Synapses, Synaptic Transmission, Ubiquitin-Protein Ligases, Ubiquitination, Zebrafish

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.

Alternate JournalNat. Methods
PubMed ID27271196
PubMed Central IDPMC5312699
Grant ListR01 AI085583 / AI / NIAID NIH HHS / United States
R01 NS081678 / NS / NINDS NIH HHS / United States
R01 GM083898 / GM / NIGMS NIH HHS / United States
R01 NS081687 / NS / NINDS NIH HHS / United States
R01 NS046579 / NS / NINDS NIH HHS / United States