2021 Nobel Prize for mechanosensory transduction

Abstract

Written by someone who has worked in the mechanobiology field for close to 40 years, this commentary describes some historical background to the recent award of one-half of the Nobel Prize for Physiology or Medicine to Ardem Patapoutian for his discovery of the family of mechanosensitive Piezo ion channels, which function as mechanoreceptors feeling the environment in senses such as touch, pain, and proprioception.

Keywords: Mechanosensitive ion channels; MscL; MscS; Piezo1; Piezo2.

Fig. 1

Piezo family of ion channels. Piezo1 and Piezo2 are members of a new family of non-selective cation channels permeable to Ca^2 + that are widely expressed in tissues of the hollow organs (lung, stomach, bladder, intestines) where they function as molecular mechanosensors. Cryo-electronmicroscopy structure of both channels revealed their curved structure in the membrane, which when flattened by mechanical force stretching the membrane, opens the channel pore (left panel). A hug is an example of the sense of touch in which Piezo2 functions as the mechanoreceptor (right panel) (Adopted and reproduced from (Ernfors et al. 2021) with permission)

Fig. 2

Preparation of and patch-clamp recording from E. coli giant spheroplasts. The major steps during generation of giant spheroplasts from E. coli (scale bar corresponds to 5 μm in all images) including generation of “snakes” and converting them into giant spheroplasts amenable to the patch clamp recording (top row). A phase contrast microphotograph of the patch pipette with a giant spheroplast at the tip (bottom row left). Activity of MscS and MscL channels of small and large conductance, respectively, recorded from an inside-out giant spheroplast patch (bottom row right). The upper trace shows the current traces of single MscS (open triangle) and MscL (filled triangle) channels opening upon application of negative pressure ramp (suction depicted by lower trace) applied to a patch pipette using a high-speed pressure clamp device. MscS activation threshold (− 114.5 mmHg) is indicated by the dotted line, whereas the activation threshold of MscL (− 195.2 mmHg) is indicated by the dashed line in good agreement with the previously reported results (Nomura et al. ; Yoshimura et al. 1999). Both MscS and MscL function as safety valves protecting bacteria from a sudden rise in cellular turgor pressure due to a hypoosmotic shock (Levina et al. 1999). Pipette potential was held at + 30 mV (Reproduced with permission from (Martinac et al. 2013))

Fig. 3

Universal phylogenetic tree. Life on Earth is organized in three kingdoms of living organisms based on small subunit tRNA sequences (Pace 1997). Examples of the mechanosensitive channels that have been identified and characterized in each kingdom are listed next to the group of organisms in which they are found (arrows). Biological timescale from the time of the Earth’s formation 4.6 billion years ago to the time of human origin (bottom right) (Woese 1994). The oldest microfossils of prokaryotic cells are approximately 3.5 billion years old (Reproduced with permission from (Martinac and Cox 2017))

Fig. 4

The discovery of Piezo channels. Piezo ion channels were discovered by using gene silencing of 72 candidate genes in the mechanosensitive mouse cell line Neuro2a and searching for a loss of mechanoreception. This enabled discovery of the Piezo ion channel family. Cryo-EM structure of the mouse Piezo1 triskelion with propeller-like arms composed of transmembrane helices forcing the membrane to curve (inset) (Reproduced and modified from (Ernfors et al. 2021) with permission)