Beyond AMPARs: Dynamic remodeling of the synaptic surface proteome during plasticity

Activity-dependent changes in synaptic strength are widely studied through mechanisms involving AMPA receptor trafficking. However, increasing evidence indicates that a broader range of synaptic membrane proteins, including neuromodulatory receptors and cell adhesion molecules, also undergo dynamic remodeling during synaptic plasticity. These proteins engage diverse trafficking and processing pathways that extend beyond classical recycling mechanisms. In this review, we discuss recent advances in two key aspects of membrane protein dynamics: compartment-specific endocytic fate decisions and the processing and delivery of locally synthesized proteins. We highlight how these pathways differ between pre- and postsynaptic compartments and contribute to distinct forms of plasticity, including LTP and LTD. Finally, we discuss emerging approaches to study synaptic surface proteome remodeling at a systems level and outline key challenges for understanding how coordinated changes in membrane protein composition shape synaptic function and plasticity.