In contrast to the plethora of cytoplasmic and membrane proteins known to regulate trafficking of excitatory glutamate receptors (Kim and Sheng, 2004; Sumioka, 2013), relatively few subcellular pathways have been described for regulating GIRK channel expression. One pathway involves a change in phosphorylation of GIRK2 channels in the hippocampus, whereby dephosphorylation of a serine residue preceding an internalization motif promotes channel recycling (Chung et al., 2009). In addition, GIRK3 channels contain a lysosomal targeting motif that can target GIRK3-containing channels for lysosomal degradation (Ma et al., 2002). Another regulatory pathway involves association of an endosomal sorting nexin 27 (SNX27) protein with GIRK channels (Balana et al., 2011; Lunn et al., 2007). Thus far, SNX27 is the only cytoplasmic protein known to selectively bind GIRK channels (Balana et al., 2011; Lunn et al., 2007).
