Graphic shows how touch- and temperature-sensitive proteins work.


Touchy-feely protein sensors

By Duncan Mil

October 6, 2021 - Discoveries of how cells detect temperature and touch at a molecular level explain how these stimuli are converted into nerve signals, enabling us to perceive and interact with the world around us.

To discover how nerve cells detect heat, David Julius at the University of California, San Francisco, exploited that capsaicin – the active component of chilli peppers in spicy food – activates heat receptors.

Julius and his team took the DNA of genes active in sensory cells and added DNA fragments to cells that were insensitive to capsaicin. From thousands of DNA fragments, they eventually isolated a single protein called TRPV1 that could make cells receptive to capsaicin.

When TRPV1 encounters a temperature rise, it opens, allowing positively-charged calcium ions (CA2+) to trigger electrical nerve signals sent to the brain to warn of the sensation of heat.

Following the discovery of TRPV1, teams led by Julius and Ardem Patapoutian at Scripps Research in La Jolla, California, independently identified a similar protein called TRPM8 that responds to cold.

Patapoutian’s team also discovered two touch receptors that act as ion channels, molecular gateways, that open or close to control the flow of charged atoms into or out of a cell. Tactile organs, Merkel cells connected to neurons (nerve fibres), are localized in fingertips and other touch-sensitive spots.

The team found large PIEZO proteins -- composed of 2,500 amino acids -- form a new class of ion channels that open in response to mechanical pressure.

The PIEZO protein has three propeller-shaped blades that curve out, creating a bowl shape around an ion-conducting pore. When a tactile stimulus is applied, the protein changes shape; the curved blades flatten out and open the central pore, allowing Merkel cells’ CA2+ to flow to the nerve fibre. Sensory neurons then fire off an electric nerve signal to the spinal cord and brain.

David Julius and Ardem Patapoutian received the 2021 Nobel Prize in Physiology or Medicine for their discoveries, leading to new treatments for a wide range of disease conditions, including chronic pain.

PUBLISHED: 06/10/2021; STORY: Graphic News