The group discovered the phenomenon while looking for neurons that control defecation. After killing the neurons innervating the posterior body muscles, the authors found that contractions nevertheless continued. To find out how, they screened for mutants in muscle contraction and identified two genes. One was pbo-5, which encodes a receptor on the muscle surface. The other was pbo-4, whose protein product sends protons out of the intestinal epithelium. Classical neurotransmitters did not activate the PBO-5 receptor or muscle contraction, but the release of caged protons did, even in pbo-4 mutants, which are unable to release their own gut protons. By contrast, pbo-5 mutants did not respond to proton release.
“These protons possess all the attributes of a classical transmitter,” says Jorgensen, including having a specific receptor. The brain might also use protons to control neuronal signaling. According to him, the gut signaling role for protons “demonstrates the creativity of evolution. Cutting out the middle man—the nervous system—allows direct communication between the epithelia and the muscle.”