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Now, using a proteomics approach, Slesinger and his team searched for proteins that might regulate the activity of GIRK3 channels and found SNX27. We knew that the GIRK3 subtype has a unique code on its tail, like a signpost, that might interact with other proteins says Slesinger.

SNX27 is a member of the sorting nexin-family, a diverse group of proteins that can bind cellular membranes and make contact with other proteins, which testifies to their role as facilitators for membrane trafficking and protein sorting. Indeed, increasing SNX27 protein in cells led to reduced GIRK activity. A closer look revealed that SNX27 colocalizes with GIRK channels in the hippocampus, a structure that plays an important role in learning and memory.

The expression of different types of GIRK channel subunits in neurons along with varying levels of specific trafficking proteins, such as SNX27, could dictate the ultimate expression levels on the surface of the plasma membrane, and therefore the strength of inhibitory signaling in the brain, says Slesinger.

Interestingly, independent researchers found previously that abused drugs such as cocaine and methamphetamine increase the activity of the SNX27 gene in rats. Changes in the expression of SNX27 may establish an important link between trafficking of GIRK channels and the action of drugs in the brain, possibly opening up new avenues for the treatment of drug addictions, says Slesinger.