CASK and FARP localize two classes of post-synaptic ACh receptors thereby promoting cholinergic transmission

Abstract

Synaptic proteins are immobilized at synapses via interactions with scaffolding proteins. Scaffolding proteins for glutamatergic and GABAergic synapses have been extensively studied; however, far less is known about how scaffolds shape the function of cholinergic synapses. Here we analyze the role of two C. elegans post-synaptic scaffolding proteins (LIN-2/CASK and FRM-3/FARP) at cholinergic neuromuscular junctions. Constitutive knockouts or muscle specific inactivation of lin-2 and frm-3 dramatically reduced spontaneous and evoked post-synaptic currents. These synaptic defects resulted from decreased abundance of post-synaptic ionotropic acetylcholine receptors (AChRs) and decreased presynaptic ACh release. Thus, our findings show that post-synaptic LIN-2/FRM-3 complexes coordinately control pre- and post-synaptic function, thereby promoting cholinergic synaptic transmission.