Curiously, overexpression of SNX27 in hippocampal neurons leads to smaller GABABR-activated GIRK currents (Balana et al., 2011), a seemingly unexpected finding in context of smaller GABABR-activated GIRK currents in VTA DA neurons lacking SNX27. Ectopic expression of SNX27 targets 5-HT4a serotonergic receptors (Joubert et al., 2004) and GIRK channels (Lunn et al., 2007) proteins to the early endosome, where it can affect the trafficking of proteins. One possibility is that high levels of SNX27 protein act as a negative regulator of forward trafficking (Lauffer et al., 2010). Previous studies have shown that abnormal levels of key endocytic proteins impair homeostasis of protein networks and disrupt activity. SNX9, for example, is able to form dimers, and therefore increased SNX9 expression has been suggested to act as a dominant negative, leading to similar defects in recycling as is observed following protein knockdown (Shin et al., 2007). Similarly, both overexpression and RNAi knockdown of SPIN90 decreased synaptic vesicle endocytosis (Kim et al., 2005). Recently, SNX27 was found to form a tripartite complex with β-Pix, which associated directly with SNX27, and indirectly with a
