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Authors & Affiliations
Wesleigh Dunn, Kirsty McMillan, Jeremy Henley, Kevin Wilkinson
Abstract
Maintaining the delicate balance between excitatory and inhibitory synaptic activity is crucial for proper brain function. The endosomal trafficking complex, retromer, plays a pivotal role in synaptic function by regulating the post-endocytic sorting of a variety of integral proteins at both excitatory and inhibitory synapses. As a result, SNX27/retromer is emerging as a potential mediator of excitatory/inhibitory crosstalk. In surface proteomic screens from primary cultured neurons, we have shown that a variety of subunits of γ-aminobutyric acid receptors (GABAARs) exhibit reduced surface expression in response to knockdown of SNX27, or the core retromer component Vps35. Furthermore, GABAA receptors co-immunoprecipitate with SNX27 from cultured neurons. Our findings indicate that GABAARs are cargos of the SNX27/retromer complex, furthering our understanding of the roles of SNX27/retromer at inhibitory synapses. We are now expanding this work to understand the role of SNX27/retromer in targeting of GABAARs to synaptic sites, how this process may be regulated by neuronal activity, and its potential implication in disease states.