Umami taste transduction: multiple receptors and pathways?

Monosodium L-glutamate (MSG), a natural component of many foods, is an important gustatory stimulus that elicits a taste quality called umami. In addition to being a potent taste stimulus, glutamate also may be a neurotransmitter at tastebud synapses. In mammalian taste buds, molecular, physiological and behavioral evidence has accumulated for the presence of ion channels gated by glutamate as well as metabotropic (G protein coupled) receptors for glutamate. Some of these may represent umami taste receptor(s), while others function to detect synaptic glutamate. To identify which glutamate receptors, if any, play a role in taste transduction, it is critical to determine if their functional properties are consistent with key features of umami taste. We have recently cloned a novel variant of the metabotropic glutamate receptor 4 (mGluR4). In situ hybridization shows that the gene is expressed in a subset of circumvallate and foliate taste buds in the rat. The variant mGluR4 contains a truncated extracellular N-terminus that dramatically alters the putative binding site for glutamate. We have functionally expressed this receptor in CHO cells, and demonstrated that it responds to glutamate. The receptor couples negatively to a cAMP cascade and displays a distinctive concentration-response relationship for glutamate, with a threshold similar to the taste threshold for MSG. Importantly, the receptor is also activated by L-AP4, a compound that mimics the taste of MSG in rats and in humans. We have termed the novel receptor taste-mGluR4. The similarities of its properties to MSG taste suggests that taste-mGluR4 is a taste receptor for glutamate.