The netrin receptor UNC-40/DCC assembles a postsynaptic scaffold and sets the synaptic content of GABA<sub>A</sub> receptors.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32471987.
- Also identified by DOI 10.1038/s41467-020-16473-5 and PMC identifier 7260190.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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<sub>A</sub>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<sub>A</sub>Rs to prepositioned NLG-1 clusters. These processes are orchestrated by the synaptic organizer CePunctin/MADD-4, which controls the localization of GABA<sub>A</sub>Rs by positioning NLG-1/neuroligin at synapses and regulates the synaptic content of GABA<sub>A</sub>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.
Medical subject headings
- Caenorhabditis elegans
- Caenorhabditis elegans Proteins
- Cell Adhesion Molecules
- Receptors, Cell Surface
- Receptors, GABA-A
- Synaptic Transmission