Commentary Cell Science Reviews Vol 5 No 4 ISSN 1742-8130

Cornichon sweetens the AMPA receptor trafficking field

AMPA receptors (AMPARs) are glutamate gated ion channels that conduct the fast excitatory currents that trigger the formation of action potentials. Neuron activity controls receptor synaptic trafficking and anchorage, thereby changing receptor synaptic abundance and regulating synaptic strength. Both the cytosolic C-terminal domains of AMPAR subunits, and receptor interactions with a family of auxiliary receptor subunits, the TARPs, contribute to this control. A recent Science paper describes a second family of AMPAR auxiliary subunits, the cornichon homologs (CNIHs), which the authors report to be the major AMPAR auxiliary subunit species. The cornichon protein was discovered in drosophila as a factor required for ER export of Gurken, a homolog of TGF-α. In mammalian neurons, the CNIHs are shown to regulate both the trafficking and physiologic properties of AMPARs, like the TARPs. However, while the TARPs have four transmembrane domains and a cytosolic C-terminus that binds scaffolds and anchors receptors at synapses, the CNIHs are predicted to have only three transmembrane domains and to lack the TARPs' ability to interact with scaffolds. This Commentary discusses mechanisms of receptor trafficking and the relative roles of AMPAR subunit domains and auxiliary subunits in regulating synapse strength. The Commentary formulates hypotheses based on CNIH structure and membrane topology about how AMPAR trafficking and synaptic abundance may be controlled.

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