An unexpected role for TMC proteins in alkaline sensing

For simple organisms, it is vital to be able to recognize dangerous pH levels in the environment. Both highly acidic and highly basic substances can be toxic if ingested, and they can injure sensitive skin.

While the molecular mechanisms for acid sensation have been well documented, far less is known about alkali sensing.

A new study by researchers at the University of Michigan Life Sciences Institute and collaborators in China identified a new type of alkaline sensor in nematodes.

The findings, published June 16 in Neuron, show that TMC-1, a part of a family of transmembrane channel-like proteins, functions as an alkali-activated channel and is required for the roundworms to detect noxiously high pH in the environment — such as alkaline soils.

The genes that encode the TMC proteins are well conserved from nematodes to humans, meaning that they have changed very little throughout evolution and are therefore likely important to key biological processes.

There are eight TMC proteins in mammals, defects in which have been implicated in conditions like hearing loss and epidermodysplasia verruciformis. The new research suggests they may also be important for alkaline sensation and/or other forms of pain avoidance, says study senior author Shawn Xu, Ph.D., the Bernard W. Agranoff Collegiate Professor at the LSI, where his lab is located, and a professor in the Department of Molecular and Integrative Physiology at the U-M Medical School.

Xu lab postdoctoral fellow Xiang Wang, Ph.D., and graduate student Guang Li were co-first authors of the paper.