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Science on the cutting eDge

The Scripps Research Institute News

Scripps Research Scientists mediator histamine. But so far, relatively little has been Curiously, the absence or enhancement of PIEZO1

Identify Sensor Underlying discovered about the circuitry of mechanical itch. activity in mice caused at least a small reduction or increase
PIEZO1’s role in mechanical itch was unexpected.

of scratching due to chemical itch triggers such as histamine –
Mechanical Itch Patapoutian won a share of last year’s Nobel Prize for implying that mechanical and chemical itch signals are indeed
Medicine or Physiology for his lab’s pioneering research
transmitted in some cases by the same sensory neurons.
Finding could lead to better drug treatments for chronic on PIEZO1 and its sister-protein PIEZO2. These unique, The researchers are now investigating whether variants of
itch conditions, like eczema. propeller-shaped “mechanosensor” ion channels are the PIEZO1 gene in the human population are related to itch
Scientists at Scripps Research have identified a protein embedded in the outer membranes of many cell types. They sensitivity. The Patapoutian lab published a paper in 2018
in sensory nerves that works as a key detector of itch – become activated when mechanically distorted, opening showing that a mildly overactive form of PIEZO1, which also
specifically the “mechanical” itch stimulus of crawling their ion channels and triggering various downstream events. has the effect of making red blood cells relatively resistant
insects, wool fibers, or other irritating objects that touch the Since 2010, Patapoutian and colleagues have shown that to malaria parasites, is present in about a third of people of
skin. PIEZO2 is a key mechanosensor for light touch, the feeling African ancestry.
The discovery published June 22, in Nature, is the first of the positioning of the body and limbs, and the urge to PIEZO1 transduces mechanical itch in mice was co-
identification of a sensor for mechanical itch rather than urinate – all via nerves in various tissues and organs. By authored by Rose Hill, Meaghan Loud, Adrienne Dubin,
chemically-triggered itch. It could lead to better treatments contrast, the researchers have found that PIEZO1 has a Brooke Peet, and Ardem Patapoutian.
for itch conditions such as eczema and psoriasis. variety of nonsensory roles throughout the body, for example Funding was provided by the Howard Hughes Medical
“These findings help us untangle the complexity of in blood vessels and red blood cells. Institute, the National Institutes of Health (R35 NS105067),
itch sensation and suggest that PIEZO1 inhibitors could While their initial studies suggested that PIEZO1 was and the Helen Hay Whitney Foundation.
be very useful clinically,” says study senior author Ardem not expressed in sensory neurons, other recent investigations
Patapoutian, Ph.D., a professor in the Department of have suggested that it is expressed at low levels in some Scientists Develop Tools For
Neuroscience at Scripps Research, and a Howard Hughes subsets of these neurons. In the new study, Patapoutian
Medical Institute investigator. and his team, including study first author Rose Hill, Ph.D., Early Detection Of SARS-
Itch is a distinct sensation with its own nerve circuitry and a postdoctoral research associate, followed up on this
evolutionary purpose – likely to alert organisms to potentially surprising lead. CoV-2 Variants In Wastewater
harmful chemicals, insects and parasites. Researchers over In experiments in mice, they confirmed that PIEZO1
the past decade or so have identified itch-specific subsets is expressed, and appears to be a functional, mechanical New tools developed at Scripps Research and U.C.
of spinal neurons that extend nerve fibers into the skin and pressure-sensitive ion channel protein in two different types San Diego are helping public health officials around the
are sensitive to chemical triggers of itch such as the allergy of sensory neuron that were already implicated in chemical world get vital information about pathogen variants from
itch. Mice with an overactive form of PIEZO1 were markedly wastewater.
more sensitive to itch sensations. By contrast, mice lacking It can be a bit smellier than other ways of monitoring
PIEZO1 in their sensory neurons scratched themselves far COVID-19, but analyzing wastewater is a cheaper, faster and
less when stimulated on the skin with filaments that normally more accurate way for public health officials and researchers
would trigger strong itch sensations. The researchers also to detect rising cases. Bits and pieces of the SARS-CoV-2
showed that a PIEZO1-blocking compound alleviates virus are flushed down toilets and washed down sinks by
scratching behaviors in mice with the equivalent of eczema. infected individuals; more copies of the virus found in
“We did see a dramatic effect on itch with this compound, sewage means more people are sick. But until now, most
and though it wasn’t specific enough against PIEZO1 wastewater analysis methods lumped all SARS-CoV-2
to develop into a drug, we hope eventually to develop a viruses together as one.
much more PIEZO1-specific compound for treating itch
conditions,” Hill says. Scripps Research on page 14