Molecular basis of junctional current rectification at an electrical synapse

Area of Science:

• Neuroscience
• Cell Biology
• Molecular Biology

Background:

• Rectifying electrical synapses (RESs) facilitate unidirectional signal transmission in neural circuits.
• The precise molecular mechanisms underlying RES rectification remain largely uncharacterized.
• In *C. elegans*, RESs between AVA interneurons and A-MNs exhibit antidromic current flow.

Purpose of the Study:

• To elucidate the mechanism of rectification in electrical synapses between AVA premotor interneurons and A-type cholinergic motoneurons (A-MNs) in *C. elegans*.
• To identify the specific innexin isoforms and molecular interactions responsible for directional current flow.

Main Methods:

• Heterologous expression of innexin isoforms (UNC-7 and UNC-9) in a non-native system.
• Analysis of junctional currents (Ij) in wild-type and mutant *C. elegans*.
• Site-directed mutagenesis of charged residues within the UNC-7b amino terminus.

Main Results:

• Only the UNC-7b isoform formed rectifying heterotypic gap junctions (GJs) with UNC-9, favoring current flow from UNC-9 to UNC-7.
• Knocking out *unc-7b* abolished junctional currents, while its AVA-specific re-expression rescued the defect.
• Mutating charged residues in the UNC-7b amino terminus eliminated the rectification property.

Conclusions:

• The UNC-7b innexin isoform is critical for establishing rectification in AVA-UNC-7b/A-MN-UNC-9 electrical synapses.
• Electrostatic interactions involving charged residues in the UNC-7b amino terminus are responsible for the observed rectification.
• This study reveals a molecular basis for directional signaling in electrical synapses.