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The netrin receptor UNC-40/DCC assembles a postsynaptic scaffold and sets the synaptic content of GABA A receptors
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The netrin receptor UNC-40/DCC assembles a postsynaptic scaffold and sets the synaptic content of GABA A receptors
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Journal Article
The netrin receptor UNC-40/DCC assembles a postsynaptic scaffold and sets the synaptic content of GABA A receptors
2020
Overview
Increasing evidence indicates that guidance molecules used during development for cellular and axonal navigation also play roles in synapse maturation and homeostasis. In C. elegans the netrin receptor UNC-40/DCC controls the growth of dendritic-like muscle cell extensions towards motoneurons and is required to recruit type A GABA receptors (GABA
Rs) at inhibitory neuromuscular junctions. Here we show that activation of UNC-40 assembles an intracellular synaptic scaffold by physically interacting with FRM-3, a FERM protein orthologous to FARP1/2. FRM-3 then recruits LIN-2, the ortholog of CASK, that binds the synaptic adhesion molecule NLG-1/Neuroligin and physically connects GABA
Rs to prepositioned NLG-1 clusters. These processes are orchestrated by the synaptic organizer CePunctin/MADD-4, which controls the localization of GABA
Rs by positioning NLG-1/neuroligin at synapses and regulates the synaptic content of GABA
Rs through the UNC-40-dependent intracellular scaffold. Since DCC is detected at GABA synapses in mammals, DCC might also tune inhibitory neurotransmission in the mammalian brain.
Subject
/ Caenorhabditis elegans - metabolism
/ Caenorhabditis elegans Proteins - metabolism
/ Cell Adhesion Molecules - metabolism
/ Cell Adhesion Molecules, Neuronal - metabolism
/ Cytoskeletal Proteins - metabolism
/ Helminth Proteins - metabolism
/ Membrane Proteins - metabolism
/ Nerve Tissue Proteins - metabolism
/ Neuromuscular Junction - metabolism
/ Receptors, Cell Surface - metabolism
