Sequences Flanking the Gephyrin-Binding Site of GlyRβ Tune Receptor Stabilization at Synapses

摘要: Abstract The efficacy of synaptic transmission is determined by the number neurotransmitter receptors at synapses. Their recruitment depends upon availability postsynaptic scaffolding molecules that interact with specific binding sequences receptor. At inhibitory synapses, gephyrin major scaffold protein mediates accumulation heteromeric glycine (GlyRs) via cytoplasmic loop in β-subunit (β-loop). This involves high- and low-affinity interactions, but molecular mechanism this bimodal its implication GlyR stabilization synapses remain unknown. We have approached question using a combination quantitative biochemical tools high-density single molecule tracking cultured rat spinal cord neurons. high-affinity site could be identified was shown to rely on formation 3 10 -helix C-terminal β-loop core gephyrin-binding motif. plays structural role shaping motif represents contributor confinement GlyRs gephyrin. N-terminal flanking sequence promotes lower affinity interactions occupying newly sites Despite low affinity, modulatory tuning mobility Together, core-binding differentially regulate receptor for trapping Our experimental approach thus bridges gap between thermodynamic aspects receptor-scaffold functional living cells.