Distinct Subunit Domains Govern Synaptic Stability and Specificity of the Kainate Receptor

• Published in: Cell reports (Cambridge) Vol. 16; no. 2; pp. 531 - 544
• Main Authors: Straub, Christoph, Noam, Yoav, Nomura, Toshihiro, Yamasaki, Miwako, Yan, Dan, Fernandes, Herman B., Zhang, Ping, Howe, James R., Watanabe, Masahiko, Contractor, Anis, Tomita, Susumu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12-07-2016; Elsevier
• Subjects: Animals; Cerebellum - cytology; Cerebellum - metabolism; Hippocampus - cytology; Hippocampus - metabolism; Mice, Transgenic; Protein Domains; Protein Stability; Protein Subunits - chemistry; Protein Subunits - physiology; Protein Transport; Receptors, Kainic Acid - chemistry; Receptors, Kainic Acid - physiology; Synapses - metabolism
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2016.05.093

Synaptic communication between neurons requires the precise localization of neurotransmitter receptors to the correct synapse type. Kainate-type glutamate receptors restrict synaptic localization that is determined by the afferent presynaptic connection. The mechanisms that govern this input-specific synaptic localization remain unclear. Here, we examine how subunit composition and specific subunit domains contribute to synaptic localization of kainate receptors. The cytoplasmic domain of the GluK2 low-affinity subunit stabilizes kainate receptors at synapses. In contrast, the extracellular domain of the GluK4/5 high-affinity subunit synergistically controls the synaptic specificity of kainate receptors through interaction with C1q-like proteins. Thus, the input-specific synaptic localization of the native kainate receptor complex involves two mechanisms that underlie specificity and stabilization of the receptor at synapses.
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•The GluK2 cytoplasmic domain mediates synaptic stabilization•Surface kainate receptor activity depends on GluK2 but not its cytoplasmic domain•The extracellular domain of high-affinity GluK subunits mediates synaptic specificity•Input-specific synaptic localization of kainate receptors is mediated by two mechanisms
Synaptic communication between neurons requires neurotransmitter receptors to be localized precisely to the correct synapse type. Straub et al. identify two distinct mechanisms that lead to input-specific synaptic localization of the kainate receptor complex in the brain.