Opening a “Wide” Window onto Taste Signal Transmission

Pubmed

From Oka Lab

How do taste buds send information to the brain?

Big unknown in the taste field is how taste bud cells communicate with peripheral sensory neurons. While taste bud cells are “innervated” by peripheral neurons, sour taste bud cells express synaptic machinery, whereas sweet, bitter, and umami cells don’t express obvious synaptic proteins.

The first clue into this handshake came from knockouts of purinergic receptors in the peripheral sensory neurons, which eliminated tastant-evoked responses. This gives the obvious hypothesis that ATP could be the neurotransmitter. Furthermore, there must be some molecule that meeiates ATP release from a taste bud cell. Indeed, prior labs in 2013 identified CALHM1 on taste bud cells as a potential ATP channel. However, as Yuki points out, CALHM1 is a bit slower in ATP release than one might expect from recording sensory neurons.

CALHM1+CALHM3 heterodimers exhibit the properties of an ATP channel

This takes us to the paper by Ma, Foskett, and collaborators. They in essence demonstrate that CALHM1 and CALHM3 form an ATP channel with the requisite properties for taste communication (e.g. necessity, sensitivity to pharmacological blockers, coexpression in taste bud cells).

There are some loose end experiments left that should be tackled, including direct measurement of ATP flux from CALHM1+3, demonstrating protein localization in the taste bud cells.

Remaining questions

The big remaining question is if all tastes are mediated by the release of ATP, then how is the selectivity achieved, as after all taste bud cells of differing taste qualities are in very close proximity to each other.