Discovery of temperature and touch receptors: An introduction of the 2021 Nobel Prize in Physiology or Medicine

Human has five senses, including vision, touch, hearing, taste, smell and taste, as well as temperature (including heat and cold) and pain sensation. How humans perceive the physical world through somatic sensation has fascinated us for centuries. The 2021 Nobel Prize in Physiology or Medicine was awarded to David Julius from the University of California, San Francisco (UCSF) and Ardem Patapoutian from Scripps Institute for their thermal and mechanical transducers discoveries. David Julius pursued a project to identify the receptor for capsaicin in the late 1990s. He screened a cDNA library from rodent dorsal root ganglia, identified a cDNA encoding a novel ion channel belonging to the superfamily of transient receptor potential (TRP) cation channels (now called TRPV1). In subsequent studies, TRPV1 demonstrated a pronounced activation by heat (especially above 40°C) and led to cellular calcium influx. Patch-clamp recordings revealed a heat-evoked membrane current similar to those of sensory neurons. Furthermore, high temperatures above 40°C have already been harmful to the human body. Because mice lacking Trpv1 showed only a minor loss of acute noxious heat sensation, other heat-sensitive receptors must exist. In 2011, Voets and his team identified TRPM3 as a second heat-sensitive receptor. In 2004, Julius noticed TRPA1, another superfamily of transient receptor potential (TRP) cation channels, can be activated by various chemical substances, as well as by cold and heat. In 2002, Julius and Patapoutian identified TRPM8 and found it can be activated by low temperature, which humans perceive as innocuous cold. At present, important roles for TRPV1, TRPA1, TRPM3, and TRPM8 in temperature sensing have been experimentally established. Thus, the discovery of TRPV1 by David Julius opened the door and represented a landmark achievement to a molecular understanding of thermosensation. Future studies will likely provide additional insights into this active research field. Ardem Patapoutian mainly focuses on the research of mechanosensitive ion channels. He identified a mechanosensitive Neuro2A cell line by using brief and rapid indentation of the plasma membrane in combination with patch-clamp recording. Ardem Patapoutian screened 72 candidate genes, including known ion channels and proteins of unknown function. The candidate genes were silenced by RNA interference one by one. Knockdown of the FAM38A, eliminated the mechanically activated current and the protein was named Piezo1. A second mechanosensitive channel Piezo2, was discovered by sequence homology. Piezo1 and Piezo2 represent an entirely novel class of ion channels as mechanical sensors. In 2014, Patapoutian found mice lacking Piezo2 in neither Merkel cells nor sensory neurons deficient in light touch sensation. Patapoutian also demonstrated that Piezo2 is the principal transduction channel for proprioception in mice. In further work, Patapoutian and his group found central roles of Piezo1 and Piezo2 for many physiological functions. The mutations in the Piezo2 gene cause several genetic disorders manifested by altered sensations of touch, vibration and proprioception in humans. The discovery of Piezo proteins provides insights into how humans perceive internal and external environments. This review focuses on the 2021 Nobel Prize in Physiology or Medicine. Recent other research on sensory perceptions is also briefly introduced.