JGP study finds that the
C. elegans orthologue of the PIEZO family is a mechanosensitive ion channel that regulates pharyngeal pumping and food sensation.The PIEZO family of mechanosensitive cation channels has been implicated in a wide variety of physiological processes in mammals and is also associated with human disease. Mammalian genomes encode two family members, known as
Piezo1 and
Piezo2, but invertebrates such as the nematode
Caenorhabditis elegans only possess a single
Piezo-related gene (
1). The function of the
C. elegans orthologue, known as
pezo-1, has largely remained obscure, but, in this issue of
JGP, Millet et al. reveal that it encodes a bona fide mechanosensitive ion channel that regulates pharyngeal activity (
2).Jonathan Millet (left), Valeria Vásquez (center), and colleagues reveal that
pezo-1, the sole PIEZO family member in
C. elegans, is a mechanosensitive ion channel that regulates pharyngeal pumping and food sensation, particularly when worms are fed with large and stiff bacterial filaments that are difficult to swallow (graphic created with BioRender.com).In 2020, an elegant study demonstrated that
pezo-1 controls
C. elegans ovulation and fertilization (
3). However, explains Valeria Vásquez from the University of Tennessee Health Science Center, whether
pezo-1 encodes for a mechanosensitive ion channel was unknown. “PEZO-1 is expressed in many tissues, including the pharynx, which is the organ we decided to concentrate on in our study,” Vásquez says.Muscle cells in the
C. elegans pharynx rhythmically contract and relax to pump food into the worm’s intestine. Vásquez and colleagues, including first author Jonathan Millet, found that PEZO-1 is expressed in several different pharyngeal cell types (
2), including the gland cells whose secretions lubricate the pharynx, and the proprioceptive NSM neurons that are thought to sense the presence of food within the pharynx lumen and release serotonin to increase the rate of pharyngeal pumping.Millet et al. analyzed pharyngeal pumping in worms lacking
pezo-1, as well as in animals expressing a
pezo-1 point mutant that, in human
Piezo1, increases channel function by slowing channel deactivation and inactivation. Loss or gain of
pezo-1 function had surprisingly little effect on pharyngeal activity, causing only mild alterations in the duration and frequency of pumping induced by serotonin, and more obvious effects when challenged with high osmolarity solutions.Worms cultured in the laboratory are usually fed a diet of small, easily ingested
Escherichia coli cells and, both loss and gain of
pezo-1 function increased the pharynx’s response to this type of food. In their natural habitat, however,
C. elegans encounter bacteria of various shapes and sizes, some of which might be harder to swallow. “It occurred to me that it might make a difference if we fed the worms with bacteria that were stiffer and longer,” Vásquez says.The researchers therefore provided their
pezo-1 mutants with
E. coli treated with cephalexin, an antibiotic that inhibits cell separation and causes the bacteria to form long, spaghetti-like filaments. Compared with wild-type worms fed with this diet, pharyngeal activity was markedly enhanced by the gain-of-function
pezo-1 mutant, but substantially reduced in the absence of
pezo-1, almost as if the worms were “choking” on the bacterial filaments.Crucially, by performing patch-clamp experiments on both cultured
C. elegans cells and insect cells expressing recombinant
pezo-1, Millet et al. confirmed that PEZO-1 is, indeed, a mechanosensitive ion channel. However, it remains to be seen exactly how PEZO-1 helps the pharynx sense the physical parameters of food and adjust its pumping activity accordingly. One possibility is that the channel acts within the proprioceptive neurons to regulate the release of serotonin.Intriguingly, the
Drosophila PIEZO orthologue controls feeding behavior in flies (
4). “However, it’s not known which mechanosensitive channels are important in the pharyngeal system of mammals,” Vásquez says. “Our studies in
C. elegans could therefore open an opportunity to understand food sensation in humans.”
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