Regulation of different phases of AMPA receptor intracellular transport by 4.1N and SAP97

Changes in the number of synaptic AMPA receptors underlie many forms of synaptic plasticity. These variations are controlled by an interplay between their intracellular transport (IT), export to the plasma membrane (PM), stabilization at synapses, and recycling. The cytosolic C-terminal domain of the AMPAR GluA1 subunit is specifically associated with 4.1 N and SAP97. We analyze how interactions between GluA1 and 4.1N or SAP97 regulate IT and exocytosis in basal conditions and after cLTP induction. The down-regulation of 4.1N or SAP97 decreases GluA1 IT properties and export to the PM. The total deletion of its C-terminal fully suppresses its IT. Our results demonstrate that during basal transmission, the binding of 4.1N to GluA1 allows their exocytosis whereas the interaction with SAP97 is essential for GluA1 IT. During cLTP, the interaction of 4.1N with GluA1 allows its IT and exocytosis. Our results identify the differential roles of 4.1N and SAP97 in the control of various phases of GluA1 IT.