All amacrine cells discriminate between heterocellular and homocellular locations when assembling connexin36-containing gap junctions

摘要

Electrical synapses (gap junctions) rapidly transmit signals between neurons and are composed of connexins. In neurons, connexin36 (Cx36) is the most abundant isoform; however, the mechanisms underlying formation of Cx36-containing electrical synapses are unknown. We focus on homocellular and heterocellular gap junctions formed by an All amacrine cell, a key intemeuron found in all mammalian retinas. In mice lacking native Cx36 but expressing a variant tagged with enhanced green fluorescent protein at the C-terminus (KO-Cx36-EGFP), heterocellular gap junctions formed between All cells and ON cone bipolar cells are fully functional, whereas homocellular gap junctions between two All cells are not formed. A tracer injected into an All amacrine cell spreads into ON cone bipolar cells but is excluded from other All cells. Reconstruction of Cx36-EGFP clusters on an All cell in the KO-Cx36-EGFP genotype confirmed that the number, but not average size, of the clusters is reduced - as expected for All cells lacking a subset of electrical synapses. Our studies indicate that some neurons exhibit at least two discriminatory mechanisms for assembling Cx36. We suggest that employing different gap-junction-forming mechanisms could provide the means for a cell to regulate its gap junctions in a target-cell-specific manner, even if these junctions contain the same connexin.