The anchoring protein SAP97 influences the trafficking and localisation of multiple membrane channels

SAP97 is a member of the MAGUK family of proteins that play a major role in the trafficking and targeting of membrane ion channels and cytosolic structural proteins in multiple cell types. Within neurons, SAP97 is localised throughout the secretory trafficking pathway and at the postsynaptic density (PSD). SAP97 differs from other MAGUK family members largely in its long N-terminus and in the sequences between the SH3 and GUK domains, where SAP97 undergoes significant alternative splicing to produce multiple SAP97 isoforms. These splice insertions endow SAP97 with differential cellular localisation patterns and functional roles within neurons. With regard to membrane ion channels, SAP97 forms multi-protein complexes with AMPA and NMDA-type glutamate receptors, and Kv1.4, Kv4.2, and Kir2.2 potassium channels, playing a major role in trafficking and anchoring ion channel surface expression. This highlights SAP97 not only as a regulator of neuronal excitability, synaptic function and plasticity in the brain, but also as a target for the pathophysiology of a number of neurological disorders. This article is part of a Special Issue entitled: Reciprocal influences between cell cytoskeleton and membrane channels, receptors and transporters. Guest Editor: Jean Claude Hervé.