Signal peptide represses GluK1 surface and synaptic trafficking through binding to amino-terminal domain.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30451858.
- Also identified by DOI 10.1038/s41467-018-07403-7 and PMC identifier 6242971.
- 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
Kainate-type glutamate receptors play critical roles in excitatory synaptic transmission and synaptic plasticity in the brain. GluK1 and GluK2 possess fundamentally different capabilities in surface trafficking as well as synaptic targeting in hippocampal CA1 neurons. Here we find that the excitatory postsynaptic currents (EPSCs) are significantly increased by the chimeric GluK1(SP<sup>GluK2</sup>) receptor, in which the signal peptide of GluK1 is replaced with that of GluK2. Coexpression of GluK1 signal peptide completely suppresses the gain in trafficking ability of GluK1(SP<sup>GluK2</sup>), indicating that the signal peptide represses receptor trafficking in a trans manner. Furthermore, we demonstrate that the signal peptide directly interacts with the amino-terminal domain (ATD) to inhibit the synaptic and surface expression of GluK1. Thus, we have uncovered a trafficking mechanism for kainate receptors and propose that the cleaved signal peptide behaves as a ligand of GluK1, through binding with the ATD, to repress forward trafficking of the receptor.
Medical subject headings
- CA1 Region, Hippocampal
- Excitatory Postsynaptic Potentials
- Protein Sorting Signals
- Kainic Acid Receptors
- Synaptic Transmission