
GluK1 カイネート受容体のアミノ末端ドメインにあるスプライス挿入は、受容体の脱感作特性、アゴニスト感受性、電位依存性ブロックなどの機能的特性を変化させる。また、これらの特性はカイネート受容体の補助タンパク質Netoタンパク質によって異なる様式で調節される。


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Kainate receptors are key modulators of synaptic transmission and plasticity in the central nervous system. Different kainate receptor isoforms with distinct spatiotemporal expressions have been identified in the brain. The GluK1-1 splice variant receptors, which are abundant in the adult brain, have an extra fifteen amino acids inserted in the amino-terminal domain (ATD) of the receptor resulting from alternative splicing of exon 9. However, the functional implications of this post-transcriptional modification are not yet clear. We employed a multi-pronged approach using cryogenic electron microscopy, electrophysiology, and other biophysical and biochemical tools to understand the structural and functional impact of this splice insert in the extracellular domain of GluK1 receptors. Our study reveals that the splice insert alters the key gating properties of GluK1 receptors and their modulation by the cognate auxiliary Neuropilin and tolloid-like (Neto) proteins 1 and 2. Mutational analysis identified the role of crucial splice residues that influence receptor properties and their modulation. Furthermore, the cryoEM structure of the variant shows that the presence of exon 9 in GluK1 does not affect the receptor architecture or domain arrangement in the desensitized state. Our study thus provides the first detailed structural and functional characterization of GluK1-1a receptors, highlighting the role of the splice insert in modulating receptor properties and their modulation.

### Competing Interest Statement

The authors have declared no competing interest.

Functional Implications of the Exon 9 Splice Insert in GluK1 Kainate Receptors

gluk1-カイネート受容体のエクソン9スプライス挿入の機能的意義


GluK1 カイネート受容体のエクソン9スプライス挿入の機能的意義
