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1.
Background
The genetic tractability and the species-specific association with beetles make the nematode Pristionchus pacificus an exciting emerging model organism for comparative studies in development and behavior. P. pacificus differs from Caenorhabditis elegans (a bacterial feeder) by its buccal teeth and the lack of pharyngeal grinders, but almost nothing is known about which genes coordinate P. pacificus feeding behaviors, such as pharyngeal pumping rate, locomotion, and fat storage.Methodology/Principal Findings
We analyzed P. pacificus pharyngeal pumping rate and locomotion behavior on and off food, as well as on different species of bacteria (Escherichia coli, Bacillus subtilis, and Caulobacter crescentus). We found that the cGMP-dependent protein kinase G (PKG) Ppa-EGL-4 in P. pacificus plays an important role in regulating the pumping rate, mouth form dimorphism, the duration of forward locomotion, and the amount of fat stored in intestine. In addition, Ppa-EGL-4 interacts with Ppa-OBI-1, a recently identified protein involved in chemosensation, to influence feeding and locomotion behavior. We also found that C. crescentus NA1000 increased pharyngeal pumping as well as fat storage in P. pacificus.Conclusions
The PKG EGL-4 has conserved functions in regulating feeding behavior in both C. elegans and P. pacificus nematodes. The Ppa-EGL-4 also has been co-opted during evolution to regulate P. pacificus mouth form dimorphism that indirectly affect pharyngeal pumping rate. Specifically, the lack of Ppa-EGL-4 function increases pharyngeal pumping, time spent in forward locomotion, and fat storage, in part as a result of higher food intake. Ppa-OBI-1 functions upstream or parallel to Ppa-EGL-4. The beetle-associated omnivorous P. pacificus respond differently to changes in food state and food quality compared to the exclusively bacteriovorous C. elegans. 相似文献2.
秀丽隐杆线虫被广泛地用作研究基因与行为关系的绝佳模式生物.线虫的咽部神经元回路控制着复杂的进食行为.为了研究进食行为的分子机制,有必要对线虫进食行为表型分析鉴定.然而,目前为止,几乎所有的线虫进食行为表型鉴定都是通过人眼来判断.因为其泵入食物的肌肉运动频率高,该行为的分析是很困难而且效率低下的.为解决这个问题,我们设计了基于计算机视觉技术的自动化成像系统来高通量分析线虫进食行为表型.此成像系统对进食表型的检测准确率达到98%以上,并使得连续可靠地分析其表型细微变化成为可能.同时,在保证高准确率的前提下单位时间内分析数据的效率比人工分析提高了3倍. 相似文献
3.
M. M. Kudelska A. Lewis C. T. Ng D. A. Doyle L. Holden-Dye V. M. O’Connor R. J. Walker 《Invertebrate neuroscience : IN》2018,18(4):14
Caenorhabditis elegans is an informative model to study the neural basis of feeding. A useful paradigm is one in which adult nematodes feed on a bacterial lawn which has been pre-loaded with pharmacological agents and the effect on pharyngeal pumping rate scored. A crucial aspect of this assay is the availability of good quality bacteria to stimulate pumping to maximal levels. A potential confound is the possibility that the pharmacological agent impacts bacterial viability and indirectly influences feeding rate. Here, the actions of nicotine on pharyngeal pumping of C. elegans and on the Escherichia coli bacterial food source were investigated. Nicotine caused an immediate and concentration-dependent inhibition of C. elegans pharyngeal pumping, IC50 4 mM (95% CI?=?3.4 mM to 4.8 mM). At concentrations between 5 and 25 mM, nicotine also affected the growth and viability of E. coli lawns. To test whether this food depletion by nicotine caused the reduced pumping, we modified the experimental paradigm. We investigated pharyngeal pumping stimulated by 10 mM 5-HT, a food ‘mimic’, before testing if nicotine still inhibited this behaviour. The IC50 for nicotine in these assays was 2.9 mM (95% CI?=?3.1 mM to 5.1 mM) indicating the depletion of food lawn does not underpin the potency of nicotine at inhibiting feeding. These studies show that the inhibitory effect of nicotine on C. elegans pharyngeal pumping is mediated by a direct effect rather than by its poorly reported bactericidal actions. 相似文献
4.
Candida M Rogers Christopher J. Franks Robert J. Walker Julian F. Burke Lindy Holden‐Dye 《Developmental neurobiology》2001,49(3):235-244
More than fifty FMRFamide‐like neuropeptides have been identified in nematodes. We addressed the role of a subset of these in the control of nematode feeding by electrophysiological recording of the activity of C. elegans pharynx. AF1 (KNEFIRFamide), AF2 (KHEYLRFamide), AF8 (KSAYMRFamide), and GAKFIRFamide (encoded by the C. elegans genes flp‐8, flp‐14, flp‐6, and flp‐5, respectively) increased pharyngeal action potential frequency, in a manner similar to 5‐HT. In contrast, SDPNFLRFamide, SADPNFLRFamide, SAEPFGTMRFamide, KPSVRFamide, APEASPFIRFamide, and AQTVRFamide (encoded by the C. elegans genes flp‐1; flp‐1; flp‐3; flp‐9; flp‐13, and flp‐16, respectively) inhibited the pharynx in a manner similar to octopamine. Only three of the neuropeptides had potent effects at low nanomolar concentrations, consistent with a physiological role in pharyngeal regulation. Therefore, we assessed whether these three peptides mediated their actions either directly on the pharynx or indirectly via the neural circuit controlling its activity by comparing actions between wild‐type and mutants with deficits in synaptic signaling. Our data support the conclusion that AF1 and SAEPFGTMRFamide regulate the activity of the pharynx indirectly, whereas APEASPFIRFamide exerts its action directly. These results are in agreement with the expression pattern for the genes encoding the neuropeptides (Kim and Li, 1999) as both flp‐8 and flp‐3 are expressed in extrapharyngeal neurons, whereas flp‐13 is expressed in I5, a neuron with synaptic output to the pharyngeal muscle. These results provide the first, direct, functional information on the action of neuropeptides in C. elegans. Furthermore, we provide evidence for a putative inhibitory peptidergic synapse, which is likely to have a role in the control of feeding. © 2001 John Wiley & Sons, Inc. J Neurobiol 49: 235–244, 2001 相似文献
5.
Ben Short 《The Journal of general physiology》2022,154(1)
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.” 相似文献
6.
Ubiquitin-mediated endocytosis and degradation of glutamate receptors controls their synaptic abundance and is implicated in modulating synaptic strength. The deubiquitinating enzymes (DUBs) that function in the nervous system are beginning to be defined, but the mechanisms that control DUB activity in vivo are understood poorly. We found previously that the DUB USP-46 deubiquitinates the Caenorhabditis elegans glutamate receptor GLR-1 and prevents its degradation in the lysosome. The WD40-repeat (WDR) proteins WDR20 and WDR48/UAF1 have been shown to bind to USP46 and stimulate its catalytic activity in other systems. Here we identify the C. elegans homologs of these WDR proteins and show that C. elegans WDR-20 and WDR-48 can bind and stimulate USP-46 catalytic activity in vitro. Overexpression of these activator proteins in vivo increases the abundance of GLR-1 in the ventral nerve cord, and this effect is further enhanced by coexpression of USP-46. Biochemical characterization indicates that this increase in GLR-1 abundance correlates with decreased levels of ubiquitin-GLR-1 conjugates, suggesting that WDR-20, WDR-48, and USP-46 function together to deubiquitinate and stabilize GLR-1 in neurons. Overexpression of WDR-20 and WDR-48 results in alterations in locomotion behavior consistent with increased glutamatergic signaling, and this effect is blocked in usp-46 loss-of-function mutants. Conversely, wdr-20 and wdr-48 loss-of-function mutants exhibit changes in locomotion behavior that are consistent with decreased glutamatergic signaling. We propose that WDR-20 and WDR-48 form a complex with USP-46 and stimulate the DUB to deubiquitinate and stabilize GLR-1 in vivo. 相似文献
7.
Kristen M. Werner Lark J. Perez Rajarshi Ghosh Martin F. Semmelhack Bonnie L. Bassler 《The Journal of biological chemistry》2014,289(38):26566-26573
In a process known as quorum sensing, bacteria use chemicals called autoinducers for cell-cell communication. Population-wide detection of autoinducers enables bacteria to orchestrate collective behaviors. In the animal kingdom detection of chemicals is vital for success in locating food, finding hosts, and avoiding predators. This behavior, termed chemotaxis, is especially well studied in the nematode Caenorhabditis elegans. Here we demonstrate that the Vibrio cholerae autoinducer (S)-3-hydroxytridecan-4-one, termed CAI-1, influences chemotaxis in C. elegans. C. elegans prefers V. cholerae that produces CAI-1 over a V. cholerae mutant defective for CAI-1 production. The position of the CAI-1 ketone moiety is the key feature driving CAI-1-directed nematode behavior. CAI-1 is detected by the C. elegans amphid sensory neuron AWCON. Laser ablation of the AWCON cell, but not other amphid sensory neurons, abolished chemoattraction to CAI-1. These analyses define the structural features of a bacterial-produced signal and the nematode chemosensory neuron that permit cross-kingdom interaction. 相似文献
8.
Jia Xu Youming Guo Tianzhuo Sui Qifei Wang Yue Zhang Ruining Zhang 《Free radical research》2017,51(5):529-544
Convallatoxin is widely used as a cardiac glycoside in acute and chronic congestive heart-failure and paroxysmal tachycardia, with many effects and underlying protective mechanisms on inflammation and cellular proliferation. However, convallatoxin has not been investigated in its antioxidant effects and lifespan extension in Caenorhabditis elegans. In this study, we found that convallatoxin (20?μM) could significantly prolong the lifespan of wild-type C. elegans up to 16.3% through daf-16, but not sir-2.1 signalling and increased thermotolerance and resistance to paraquat-induced oxidative stress. Convallatoxin also improved pharyngeal pumping, locomotion, reduced lipofuscin accumulation and reactive oxygen species levels in C. elegans, which were attributed to hormesis, free radical-scavenging effects in vivo, and up-regulation of stress resistance-related proteins, such as SOD-3 and HSP-16.1. Furthermore, aging-associated genes daf-16, sod-3, and ctl-2 also appeared to contribute to the stress-resistance effect of convallatoxin. In summary, this study demonstrates that convallatoxin can protect against heat and oxidative stress and extend the lifespan of C. elegans, pointing it as a potential novel drug for retarding the aging process in humans. 相似文献
9.
James Dillon Ioannis Andrianakis Kate Bull Steve Glautier Vincent O'Connor Lindy Holden-Dye Christopher James 《PloS one》2009,4(12)
Background
The pharyngeal microcircuit of the nematode Caenorhabditis elegans serves as a model for analysing neural network activity and is amenable to electrophysiological recording techniques. One such technique is the electropharyngeogram (EPG) which has provided insight into the genetic basis of feeding behaviour, neurotransmission and muscle excitability. However, the detailed manual analysis of the digital recordings necessary to identify subtle differences in activity that reflect modulatory changes within the underlying network is time consuming and low throughput. To address this we have developed an automated system for the high-throughput and discrete analysis of EPG recordings (AutoEPG).Methodology/Principal Findings
AutoEPG employs a tailor made signal processing algorithm that automatically detects different features of the EPG signal including those that report on the relaxation and contraction of the muscle and neuronal activity. Manual verification of the detection algorithm has demonstrated AutoEPG is capable of very high levels of accuracy. We have further validated the software by analysing existing mutant strains with known pharyngeal phenotypes detectable by the EPG. In doing so, we have more precisely defined an evolutionarily conserved role for the calcium-dependent potassium channel, SLO-1, in modulating the rhythmic activity of neural networks.Conclusions/Significance
AutoEPG enables the consistent analysis of EPG recordings, significantly increases analysis throughput and allows the robust identification of subtle changes in the electrical activity of the pharyngeal nervous system. It is anticipated that AutoEPG will further add to the experimental tractability of the C. elegans pharynx as a model neural circuit. 相似文献10.
Yiwen Zhou John R. Falck Michael Rothe Wolf-Hagen Schunck Ralph Menzel 《Journal of lipid research》2015,56(11):2110-2123
Cytochrome P450 (CYP)-dependent eicosanoids comprise epoxy- and hydroxy-metabolites of long-chain PUFAs (LC-PUFAs). In mammals, CYP eicosanoids contribute to the regulation of cardiovascular and renal function. Caenorhabditis elegans produces a large set of CYP eicosanoids; however, their role in worm’s physiology is widely unknown. Mutant strains deficient in LC-PUFA/eicosanoid biosynthesis displayed reduced pharyngeal pumping frequencies. This impairment was rescued by long-term eicosapentaenoic and/or arachidonic acid supplementation, but not with a nonmetabolizable LC-PUFA analog. Short-term treatment with 17,18-epoxyeicosatetraenoic acid (17,18-EEQ), the most abundant CYP eicosanoid in C. elegans, was as effective as long-term LC-PUFA supplementation in the mutant strains. In contrast, 20-HETE caused decreased pumping frequencies. The opposite effects of 17,18-EEQ and 20-HETE were mirrored by the actions of neurohormones. 17,18-EEQ mimicked the stimulating effect of serotonin when added to starved worms, whereas 20-HETE shared the inhibitory effect of octopamine in the presence of abundant food. In wild-type worms, serotonin increased free 17,18-EEQ levels, whereas octopamine selectively induced the synthesis of hydroxy-metabolites. These results suggest that CYP eicosanoids may serve as second messengers in the regulation of pharyngeal pumping and food uptake in C. elegans. 相似文献
11.
Sylvana Papaioannou David Marsden Christopher J. Franks Robert J. Walker Lindy Holden‐Dye 《Developmental neurobiology》2005,65(3):304-319
The nervous system of C. elegans has a remarkable abundance of flp genes encoding FMRFamide‐like (FLP) neuropeptides. To provide insight into the physiological relevance of this neuropeptide diversity, we have tested more than 30 FLPs (encoded by 23 flps) for bioactivity on C. elegans pharynx. Eleven flp genes encode peptides that inhibit pharyngeal activity, while eight flp genes encode peptides that are excitatory. Three potent peptides (inhibitory, FLP‐13A, APEASPFIRFamide; excitatory, FLP‐17A, KSAFVRFamide; excitatory, FLP‐17B, KSQYIRFamide) are encoded by flp genes, which, according to reporter gene constructs, are expressed in pharyngeal motoneurons. Thus, they may act through receptors localized on the pharyngeal muscle. The two other potent peptides, FLP‐8 (excitatory AF1, KNEFIRFamide,) and FLP‐11A (inhibitory, AMRNALVRFamide), appear to be expressed in extrapharyngeal neurons and are therefore likely to act either indirectly or as neurohormones. Intriguingly, a single neuron can express peptides that have potent but opposing biological activity in the pharynx. Only five flp genes encode neuropeptides that have no observable effect on the pharynx, but none of these have shown reporter gene expression in the pharyngeal nervous system. To examine the roles of multiple peptides produced from single precursors, a comparison was made between the bioactivity of different neuropeptides for five flp genes (flp‐3, flp‐13, flp‐14, flp‐17, and flp‐18). For all but one gene (flp‐14), the effects of peptides encoded by the same gene were similar. Overall, this study demonstrates the impressive neurochemical complexity of the simple circuit that regulates feeding in the nematode, C. elegans. © 2005 Wiley Periodicals, Inc. J Neurobiol, 2005 相似文献
12.
《Bioscience, biotechnology, and biochemistry》2013,77(11):2361-2365
In reverse genetics, RNA interference (RNAi) which is substitutable for gene-disruption, is an outstanding method for knockdown of a gene’s function. In Caenorhabditis elegans, feeding RNAi is most convenient, but this RNAi is not suitable for knockdown of multiple genes. Hence, we attempted to establish an efficient method of feeding RNAi for multiple knockdown. We produced bacteria yielding three distinct double-stranded RNAs bound to one another, and fed those bacteria to C. elegans. Quantitative RT-PCR and observation of phenotypes indicated that our method is much more efficient than the traditional one. Our method is useful for investigating genes’ functions in C. elegans. 相似文献
13.
Christopher J. Franks Caitriona Murray David Ogden Vincent O’Connor Lindy Holden-Dye 《Invertebrate neuroscience : IN》2009,9(1):43-56
Dissecting the function of neural circuits requires the capability to stimulate and record from the component neurones. Optimally,
the methods employed should enable precise activation of distinct elements within the circuit and high-fidelity readout of
the neuronal response. Here we compare two methods for neural stimulation in the pharyngeal system of Caenorhabditis elegans by evoking postsynaptic potentials (PSPs) either by electrical stimulation or by expression of the channelrhodopsin [ChR2(gf)]
in cholinergic neurones of the pharyngeal circuit. Using a dissection that isolates the pharynx and its embedded neural system
of 20 neurones permits analysis of the neurotransmitter pathways within this microcircuit. We describe protocols for selective
electrically evoked or ChR2-mediated cholinergic synaptic events in this circuit. The latter was achieved by generating strains,
punc-17::ChR2(gf);yfp, that express ChR2(gf) in cholinergic neurones. PSPs evoked by both electrical and light stimulation exhibited a rapid time-course
and were blocked by cholinergic receptor antagonists and rapidly reversed on cessation of the stimulus. Electrically evoked
PSPs were also reduced in a hypomorphic mutant for the synaptic vesicle acetylcholine transporter, unc-17, further indicating they are nicotinic cholinergic PSPs. The pharyngeal nervous system is exquisitely sensitive to both electrical
and light activation. For the latter, short light pulses of 200 μs delivered to punc-17::ChR2(gf);yfp are capable of generating full muscle action potentials. We conclude that the application of optogenetic approaches to the
C. elegans isolated pharynx preparation opens the way for a precise molecular dissection of synaptic events in the pharyngeal microcircuit
by providing a molecular and system level analysis of the synapses that control the feeding behaviour of C. elegans. 相似文献
14.
Yang Zhao Liang Zhao Xiaonan Zheng Tianjiao Fu Huiyuan Guo Fazheng Ren 《Journal of microbiology (Seoul, Korea)》2013,51(2):183-188
In this study, we utilized the nematode Caenorhabditis elegans to assess potential life-expanding effect of Lactobacillus salivarius strain FDB89 (FDB89) isolated from feces of centenarians in Bama County (Guangxi, China). This study showed that feeding FDB89 extended the mean life span in C. elegans by up to 11.9% compared to that of control nematodes. The reduced reproductive capacities, pharyngeal pumping rate, growth, and increased superoxide dismutase (SOD) activity and XTT reduction capacity were also observed in FDB89 feeding worms. To probe the anti-aging mechanism further, we incorporated a food gradient feeding assay and assayed the life span of eat-2 mutant. The results demonstrated that the maximal life span of C. elegans fed on FDB89 was achieved at the concentration of 1.0 mg bacterial cells/plate, which was 10-fold greater than that of C. elegans fed on E. coli OP50 (0.1 mg bacterial cells/plate). However, feeding FDB89 could not further extend the life span of eat-2 mutant. These results indicated that FDB89 modulated the longevity of C. elegans in a dietary restriction-dependent manner and expanded the understanding of anti-aging effect of probiotics. 相似文献
15.
16.
Jessica Dysarz Georg Fuellen Steffen Mller Walter Luyten Christian Schmitz-Linneweber Nadine Saul 《Biology letters》2021,17(6)
Recently, nine Caenorhabditis elegans genes, grouped into two pathways/clusters, were found to be implicated in healthspan in C. elegans and their homologues in humans, based on literature curation, WormBase data mining and bioinformatics analyses. Here, we further validated these genes experimentally in C. elegans. We downregulated the nine genes via RNA interference (RNAi), and their effects on physical function (locomotion in a swim assay) and on physiological function (survival after heat stress) were analysed in aged nematodes. Swim performance was negatively affected by the downregulation of acox-1.1, pept-1, pak-2, gsk-3 and C25G6.3 in worms with advanced age (twelfth day of adulthood) and heat stress resistance was decreased by RNAi targeting of acox-1.1, daf-22, cat-4, pig-1, pak-2, gsk-3 and C25G6.3 in moderately (seventh day of adulthood) or advanced aged nematodes. Only one gene, sad-1, could not be linked to a health-related function in C. elegans with the bioassays we selected. Thus, most of the healthspan genes could be re-confirmed by health measurements in old worms. 相似文献
17.
18.
This review considers the factors involved in the regulation of feeding and metabolism in response to food deprivation using
Caenorhabditis elegans as a model organism. Some of the sensory neurons and interneurons involved in food intake are described, together with an
overview of pharyngeal pumping. A number of chemical transmitters control feeding in C. elegans including 5-hydroxytryptamine (5-HT, serotonin), acetylcholine, glutamate, dopamine, octopamine, and tyramine. The roles
of these transmitters are modified by neuropeptides, including FMRFamide-like peptides (FLPs), neuropeptide-like protein (NLPs),
and insulin-like peptides. The precise effects of many of these neuropeptides have yet to be elucidated but increasingly they
are being shown to play a role in feeding and metabolism in C. elegans. The regulation of fat stores is complex and appears to involve the expression of a large number of genes, many with mammalian
homologues, suggesting that fat regulatory signalling is conserved across phyla. Finally, a brief comparison is made between
C. elegans and mammals where for both, despite their evolutionary distance, classical transmitters and neuropeptides have anorectic
or orexigenic properties. Thus, there is a rationale to support the argument that an understanding of the molecular and genetic
basis of feeding and fat regulation in C. elegans may contribute to efforts aimed at the identification of targets for the treatment of conditions associated with abnormal
metabolism and obesity. 相似文献
19.
20.
Jonathan R.M. Millet Luis O. Romero Jungsoo Lee Briar Bell Valeria Vsquez 《The Journal of general physiology》2022,154(1)
PIEZO channels are force sensors essential for physiological processes, including baroreception and proprioception. The Caenorhabditis elegans genome encodes an orthologue gene of the Piezo family, pezo-1, which is expressed in several tissues, including the pharynx. This myogenic pump is an essential component of the C. elegans alimentary canal, whose contraction and relaxation are modulated by mechanical stimulation elicited by food content. Whether pezo-1 encodes a mechanosensitive ion channel and contributes to pharyngeal function remains unknown. Here, we leverage genome editing, genetics, microfluidics, and electropharyngeogram recording to establish that pezo-1 is expressed in the pharynx, including in a proprioceptive-like neuron, and regulates pharyngeal function. Knockout (KO) and gain-of-function (GOF) mutants reveal that pezo-1 is involved in fine-tuning pharyngeal pumping frequency, as well as sensing osmolarity and food mechanical properties. Using pressure-clamp experiments in primary C. elegans embryo cultures, we determine that pezo-1 KO cells do not display mechanosensitive currents, whereas cells expressing wild-type or GOF PEZO-1 exhibit mechanosensitivity. Moreover, infecting the Spodoptera frugiperda cell line with a baculovirus containing the G-isoform of pezo-1 (among the longest isoforms) demonstrates that pezo-1 encodes a mechanosensitive channel. Our findings reveal that pezo-1 is a mechanosensitive ion channel that regulates food sensation in worms. 相似文献