The atypical hippocampal' glutamate receptor coupled to phospholipase D that controls stretch-sensitivity in primary mechanosensory nerve endings is homomeric purely metabotropic GluK2

A metabotropic glutamate receptor coupled to phospholipase D (PLD-mGluR) was discovered in the hippocampus over three decades ago. Its pharmacology and direct linkage to PLD activation are well established and indicate it is a highly atypical glutamate receptor. A receptor with the same pharmacology is present in spindle primary sensory terminals where its blockade can totally abolish, and its activation can double, the normal stretch-evoked firing. We report here the first identification of this PLD-mGluR protein, by capitalizing on its expression in primary mechanosensory terminals, developing an enriched source, pharmacological profiling to identify an optimal ligand, and then functionalizing it as a molecular tool. Evidence from immunofluorescence, western and far-western blotting indicates PLD-mGluR is homomeric GluK2, since GluK2 is the only glutamate receptor protein/receptor subunit present in spindle mechanosensory terminals. Its expression was also found in the lanceolate palisade ending of hair follicle, also known to contain the PLD-mGluR. Finally, in a mouse model with ionotropic function ablated in the GluK2 subunit, spindle glutamatergic responses were still present, confirming it acts purely metabotropically. We conclude the PLD-mGluR is a homomeric GluK2 kainate receptor signalling purely metabotropically and it is common to other, perhaps all, primary mechanosensory endings.New FindingsWhat is the central question of this study? The metabotropic glutamate receptor coupled to phospholipase D (PLD-mGluR) is a glutamate receptor previously only characterized pharmacologically but essential for maintaining stretch responsiveness in muscle spindle mechanosensory primary endings: what is the PLD-mGluR protein?What is the main finding and its importance?PLD-mGluR was identified as a homomeric GluK2 receptor signalling metabotropically. This identifies PLD-mGluR 30 years after its discovery. This is important because: PLD-mGluR is essential for muscle spindle stretch sensitivity; it is the first native kainate receptor shown to signal solely metabotropically; and, as it is the only GluR expressed in spindle mechanosensory endings, muscle spindles make a good functional assay of the native receptor.

Automated summary

The metabotropic glutamate receptor coupled to phospholipase D (PLD-mGluR) has been identified as a homomeric GluK2 receptor signaling metabotropically. This finding is significant because it helps us better understand the role and importance of PLD-mGluR in muscle spindle mechanosensory primary endings.