Ardem Patapoutian and David Julius have received the 2021 Nobel Prize in Physiology or Medicine for their work deciphering how our body’s cells sense temperature and touch.
The pressure of touch
Ardem Patapoutian’s work at Scripps Research, California, identified Piezo1 and Piezo2 as essential components in mechanically activated (MA) channels.1 This ground-breaking research showed how Piezo1 and Piezo2, which are multipass transmembrane proteins, are required for mechanically stimulated cation conductance to occur in response to pressure. These channels are present in the skin and other organs and you can find similar proteins expressed across diverse species from protozoa to vertebrates.
With mounting interest, Patapoutian and colleagues wanted to understand these proteins in more detail, but X-ray crystallography and NMR spectroscopy were unlikely to cope with the huge size of the Piezo proteins – Piezo1 for example is a whopping 300 kDa. Thankfully, with the aid of electron cryo-microscopy, Patapoutiain and collaborators defined the structure of Piezo1 in more detail than earlier efforts had managed.2
Patapoutian’s work paved the way for an explosion of research in MA and mechanosensitive channels, with hundreds of papers being devoted to studying Piezo channels alone.
David Julius, at the University of California in San Francisco (UCSF), on the other hand, was looking at the mechanisms behind pain. Julius used capsaicin – the molecule responsible for the fiery taste in your chili – due to its ability to induce the sensation of heat and burning. This work eventually led to the discovery of TRPV1, the receptor for capsaicin, which is activated as temperature increases and is thus a transducer of painful heat stimuli.3
As TRPV1 become increasingly well-known and examined, David Julius went on to work with biophysicist Yifan Cheng to describe TRPV1 in never-before-seen detail using electron cryo-microscopy.4
Julius’ work also extended to other areas of sensory research. This ranged from understanding how venom-derived toxins activate nociceptive neural pathways by targeting somatosensory nerve terminals,5 to how enterochromaffin cells express voltage-gated ion channels and sensory receptors to detect and relay information about the environment and metabolism from the gut directly to the nervous system.6
The Importance of Sense
The work of Patapoutian and Julius is so important because the ability to sense touch and temperature underlies how almost every tissue and cell type functions. Being able to avoid painful stimuli, like heat, or interact with the environment, has been critical for organisms to evolve survive. Internally, we rely on our bodies to correctly determine and respond to events such as changes in blood and air pressure, or how full a bladder or bowel is.
The essence of sense pervades so much of what we experience on a macro-level and how cells respond and behave on a micro-level. Patapoutain and Julius’ research not only elevates our basic understanding of these processes but has real implications in the world of medicine and rehabilitation.
Reagents Behind the Research
In the same way all good research relies on the work of multiple people, good research also rests on the shoulders of great reagents. The lab of David Julius has made use of a range of Alomone reagents over the years. We are so incredibly proud to be providing robust and reliable reagents to researchers that have had such a positive impact on the field.
Membranes proteins have been our focus for decades and we’re happy to say that with us you can find one of the most comprehensive collections of reagents in this field. So, we thought we’d share with you some exciting tools you might like to use in your research.
As membrane protein specialists, we have some of the most highly cited, validated, and characterized antibodies in this area, many of which are independently knock-out validated. These include
- Anti-TRPV1 (VR1) Antibody (#ACC-030)
- Anti-TRPM8 (extracellular) Antibody (#ACC-049)
- Anti-Piezo1 Antibody (#APC-087)
- Anti-Piezo2 Antibody (#APC-090)
You can also access an anti-TRPV1 antibody that specifically recognizes the extracellular region of the human channel, and so gives you the ability to study its expression on living cells:
You can even get it conjugated to FITC for flow cytometry studies:
Toxins and Small Molecules
Toxins are incredibly powerful tools that give you the ability to modulate specific ion channels.
- ProTx-I (#STP-400) to block NaV, CaV3.1, KV2.1 and TRPA1 channels
- Wasabi Receptor Toxin (#STW-200) to activate TRPA1 Channel
- SKF 96365 hydrochloride (#S-175) to block CaV3 and TRPC channels
- Resiniferatoxin (#R-400) to activate the TRPV1 channel
- Capsaicin (#C-125) to activate the TRPV1 channel
- GsMTx-4 (#STG-100) to block NaV1.7, TRPC1, TRPC6, and Piezo1 channels
We can’t guarantee a Nobel prize but having reagents you can rely on can only ever be a good thing.
- Coste, B. et al. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science (80-. ). 330, 55–60 (2010).
- Saotome, K. et al. Structure of the mechanically activated ion channel Piezo1. Nature 554, 481–486 (2018).
- Caterina, M. J. et al. The capsaicin receptor: A heat-activated ion channel in the pain pathway. Nature 389, 816–824 (1997).
- Liao, M., Cao, E., Julius, D. & Cheng, Y. Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature 504, 107–112 (2013).
- Bohlen, C. J. & Julius, D. Receptor-targeting mechanisms of pain-causing toxins: How ow? Toxicon 60, 254–264 (2012).
- Beumer, J. & Clevers, H. How the Gut Feels, Smells, and Talks. Cell 170, 10–11 (2017).
Photo by Claudio Schwarz.