Luo J et al. (2009) Genetics "The Caenorhabditis elegans ing-3 gene regulates ionizing radiation-induced germ-cell apoptosis in a p53-associated pathway."

Shah S, Luo J, Mains PE, Riabowol K

[Genetics, 2009]

The INhibitor of Growth (ING) family of type II tumor suppressors are encoded by five genes in mammals and three genes in C. elegans. All ING proteins contain a highly conserved plant homeodomain zinc finger (PHD). ING proteins are activated by stresses, including ionizing radiation, leading to the activation of p53. ING proteins in mammals and yeast have recently been shown to read the histone code in a methylation-sensitive manner, targeting histone acetyltransferase (HAT) and histone deacetylase (HDAC) complexes to chromatin and subsequently regulate gene expression. Here we identify and characterize ing-3, the C. elegans gene with the highest sequence identity to the human ING3 gene. ING-3 co-localizes with chromatin in embryos, germ line and somatic cells. The ing-3 gene is part of an operon but is also transcribed from its own promoter. Both ing-3(RNAi) and ing-3 mutant strains demonstrate that the gene likely functions in the same pathway as the C. elegans p53 homolog, cep-1, to induce germ cell apoptosis in response to ionizing radiation. Somatically, the ing-3 mutant has a weak kinker phenotype.

Luo J et al. (2021) Curr Biol "Sex-specific, pdfr-1-dependent modulation of pheromone avoidance by food abundance enables flexibility in C.elegans foraging behavior."

Portman DS, Luo J

[Curr Biol, 2021]

To make adaptive feeding and foraging decisions, animals must integrate diverse sensory streams with multiple dimensions of internal state. In C.elegans, foraging and dispersal behaviors are influenced by food abundance, population density, and biological sex, but the neural and genetic mechanisms that integrate these signals are poorly understood. Here, by systematically varying food abundance, we find that chronic avoidance of the population-density pheromone ascr#3 is modulated by food thickness, such that hermaphrodites avoid ascr#3 only when food is scarce. The integration of food and pheromone signals requires the conserved neuropeptide receptor PDFR-1, as pdfr-1 mutant hermaphrodites display strong ascr#3 avoidance, even when food is abundant. Conversely, increasing PDFR-1 signaling inhibits ascr#3 aversion when food is sparse, indicating that this signal encodes information about food abundance. In both wild-type and pdfr-1 hermaphrodites, chronic ascr#3 avoidance requires the ASI sensory neurons. In contrast, PDFR-1 acts in interneurons, suggesting that it modulates processing of the ascr#3 signal. Although a sex-shared mechanism mediates ascr#3 avoidance, food thickness modulates this behavior only in hermaphrodites, indicating that PDFR-1 signaling has distinct functions in the two sexes. Supporting the idea that this mechanism modulates foraging behavior, ascr#3 promotes ASI-dependent dispersal of hermaphrodites from food, an effect that is markedly enhanced when food is scarce. Together, these findings identify a neurogenetic mechanism that sex-specifically integrates population and food abundance, two important dimensions of environmental quality, to optimize foraging decisions. Further, they suggest that modulation of attention to sensory signals could be an ancient, conserved function of pdfr-1.

Luo J et al. (2015) Genetics "Neuropeptide receptors NPR-1 and NPR-2 regulate Caenorhabditis elegans avoidance response to the plant stress hormone methyl salicylate."

Tan Z, Xu Z, Luo J, Zhang Z, Ma L

[Genetics, 2015]

Methyl salicylate (MeSa) is a stress hormone released by plants under attack by pathogens or herbivores . MeSa has been shown to attract predatory insects of herbivores and repel pests. The molecules and neurons underlying animal response to MeSa are not known. Here we found that the nematode Caenorhabditis elegans exhibits a strong avoidance response to MeSa, which requires the activities of two closely related neuropeptide receptors NPR-1 and NPR-2. Molecular analyses suggest that NPR-1 expressed in the RMG inter/motor neurons is required for MeSa avoidance. An NPR-1 ligand FLP-18 is also required. Using a rescuing npr-2 promoter to drive a GFP transgene, we identified that NPR-2 is expressed in multiple sensory and interneurons. Genetic rescue experiments suggest that NPR-2 expressed in the AIZ interneurons is required for MeSa avoidance. We also provide evidence that the AWB sensory neurons might act upstream of RMGs and AIZs to detect MeSa. Our results suggest that NPR-2 has an important role in regulating animal behavior and that NPR-1 and NPR-2 act on distinct interneurons to affect C. elegans avoidance response to MeSa.

Luo, J. et al. (2017) International Worm Meeting "Genetic sex acts through the DM gene mab-3 to promote sex differences in C. elegans pheromone attraction."

Luo, J., Schroeder, F., Fagan, K., Portman, D.

[International Worm Meeting, 2017]

Sex differences in behavior provide an opportunity to understand how a single genetic cue modulates neural circuit development, function, and behavior. In C. elegans, males are potently attracted to some ascaroside pheromones, particularly ascr#3 (C9), while hermaphrodites are repelled. Using neuron-specific genetic sex reversal, we screened sensory neuron classes that might be involved in male pheromone attraction. We found that the sexual state of the shared sensory neuron ADF determines the behavioral response to ascr#3: masculinization of ADF generates robust ascr#3 attraction in hermaphrodites, while feminization of ADF abolishes attraction in males. The C. elegans sex determination pathway acts through the master regulator tra-1, whose activity specifies the hermaphrodite state. To ask how tra-1 regulates ADF's properties, we focused on the DM-domain transcription factor mab-3, which is known to be male-specifically expressed in ADF. We found that mab-3(lf) mutants were moderately defective in ascr#3 attraction, while hermaphrodites were unaffected. mab-3 function requires ADF, as mab-3(lf) had no effect in ADF-ablated males. Moreover, ADF-specific expression of mab-3 rescued the mab-3 mutant phenotype. Thus mab-3 likely acts downstream of tra-1 to promote ADF's male-specific properties. Consistent with this, we found that mab-3 is partially required for the ascr#3 attraction seen in ADF-masculinized hermaphrodites. However, because ADF-dependent sex differences still exist in mab-3 mutants, tra-1 likely has additional targets in this cell. We are currently working to understand how mab-3 controls sex differences in ADF function and to identify factors responsible for the mab-3-independent sex differences in this cell.

Luo J et al. (2024) Curr Biol "C. elegans males optimize mate-preference decisions via sex-specific responses to multimodal sensory cues."

Bainbridge C, Luo J, Portman DS, Miller RM, Barrios A

[Curr Biol, 2024]

For sexually reproducing animals, selecting optimal mates is important for maximizing reproductive fitness. In the nematode C. elegans, populations reproduce largely by hermaphrodite self-fertilization, but the cross-fertilization of hermaphrodites by males also occurs. Males' ability to recognize hermaphrodites involves several sensory cues, but an integrated view of the ways males use these cues in their native context to assess characteristics of potential mates has been elusive. Here, we examine the mate-preference behavior of C. elegans males evoked by natively produced cues. We find that males use a combination of volatile sex pheromones (VSPs), ascaroside sex pheromones, surface-associated cues, and other signals to assess multiple features of potential mates. Specific aspects of mate preference are communicated by distinct signals: developmental stage and sex are signaled by ascaroside pheromones and surface cues, whereas the presence of a self-sperm-depleted hermaphrodite is likely signaled by VSPs. Furthermore, males prefer to interact with virgin over mated, and well-fed over food-deprived, hermaphrodites; these preferences are likely adaptive and are also mediated by ascarosides and other cues. Sex-typical mate-preference behavior depends on the sexual state of the nervous system, such that pan-neuronal genetic masculinization in hermaphrodites generates male-typical social behavior. We also identify an unexpected role for the sex-shared ASH sensory neurons in male attraction to ascaroside sex pheromones. Our findings lead to an integrated view in which the distinct physical properties of various mate-preference cues guide a flexible, stepwise behavioral program by which males assess multiple features of potential mates to optimize mate preference.

Luo J et al. (2017) PLoS One "Baicalin inhibits biofilm formation, attenuates the quorum sensing-controlled virulence and enhances Pseudomonas aeruginosa clearance in a mouse peritoneal implant infection model."

Luo J, Kong J, Lei D, Chen Y, Li Y, Wang K, Cai S, Liu T, Dong B, Cheng X

[PLoS One, 2017]

The quorum sensing (QS) circuit plays a role in the precise regulation of genes controlling virulence factors and biofilm formation in Pseudomonas aeruginosa. QS-controlled biofilm formation by Pseudomonas aeruginosa in clinical settings has remained controversial due to emerging drug resistance; therefore, screening diverse compounds for anti-biofilm or anti-QS activities is important. This study demonstrates the ability of sub-minimum inhibitory concentrations (sub-MICs) of baicalin, an active natural compound extracted from the traditional Chinese medicinal Scutellaria baicalensis, to inhibit the formation of Pseudomonas aeruginosa biofilms and enhance the bactericidal effects of various conventional antibiotics in vitro. In addition, baicalin exerted dose-dependent inhibitory effects on virulence phenotypes (LasA protease, LasB elastase, pyocyanin, rhamnolipid, motilities and exotoxin A) regulated by QS in Pseudomonas aeruginosa. Moreover, the expression levels of QS-regulatory genes, including lasI, lasR, rhlI, rhlR, pqsR and pqsA, were repressed after sub-MIC baicalin treatment, resulting in significant decreases in the QS signaling molecules 3-oxo-C12-HSL and C4-HSL, confirming the ability of baicalin-mediated QS inhibition to alter gene and protein expression. In vivo experiments indicated that baicalin treatment reduces Pseudomonas aeruginosa pathogenicity in Caenorhabditis elegans. Greater worm survival in the baicalin-treated group manifested as an increase in the LT50 from 24 to 96 h. In a mouse peritoneal implant infection model, baicalin treatment enhanced the clearance of Pseudomonas aeruginosa from the implants of mice infected with Pseudomonas aeruginosa compared with the control group. Moreover, the combination of baicalin and antibiotics significantly reduced the numbers of colony-forming units in the implants to a significantly greater degree than antibiotic treatment alone. Pathological and histological analyses revealed mitigation of the inflammatory response and reduced cell infiltration in the peritoneal tissue surrounding the implants after baicalin treatment. Measurement of the cytokine levels in the peritoneal lavage fluid of mice in the baicalin treatment group revealed a decrease in IL-4, an increase in interferon (IFN-), and a reversed IFN-/IL-4 ratio compared with the control group, indicating that baicalin treatment activated the Th1-induced immune response to expedite bacterial load clearance. Based on these results, baicalin might be a potent QS inhibitor and anti-biofilm agent for combating Pseudomonas aeruginosa biofilm-related infections.

Luo S et al. (2006) J Biol "Regulators of kinesin involved in polarized trafficking and axon outgrowth."

Nonet ML, Luo S

[J Biol, 2006]

ABSTRACT : Proteins such as UNC-76 that associate with kinesin motors are important in directing neurite extension. A small Caenorhabditis elegans coiled-coil protein, UNC-69, has now been shown to interact with UNC-76 and to be involved in axonal (but not dendritic) transport and outgrowth, as well as synapse formation.

Luo L et al. (2006) J Exp Biol "Sensorimotor control during isothermal tracking in Caenorhabditis elegans."

Luo L, Clark DA, Mahadevan L, Biron D, Samuel AD

[J Exp Biol, 2006]

In order to purposefully navigate their environments, animals rely on precise coordination between their sensory and motor systems. The integrated performance of circuits for sensorimotor control may be analyzed by quantifying an animal''s motile behavior in defined sensory environments. Here, we analyze the ability of the nematode C. elegans to crawl isothermally in spatial thermal gradients by quantifying the trajectories of individual worms responding to defined spatiotemporal thermal gradients. We show that sensorimotor control during isothermal tracking may be summarized as a strategy in which the worm changes the curvature of its propulsive undulations in response to temperature changes measured at its head. We show that a concise mathematical model for this strategy for sensorimotor control is consistent with the exquisite stability of the worm''s isothermal alignment in spatial thermal gradients as well as its more complex trajectories in spatiotemporal thermal gradients.

Luo T et al. (2018) J Invertebr Pathol "Nematodes avoid and are killed by Bacillus mycoides-produced styrene."

Yang L, Hou S, Qi G, Luo T, Zhao X

[J Invertebr Pathol, 2018]

Root-knot nematodes are obligate parasites that feed on plant roots and cause serious crop losses worldwide. Bacillus species (Bacilliaceae) can produce nematicidal metabolites and have shown good potential for biological control of nematodes. In this study, Bacillus mycoides strain R2 isolated from rhizosphere soil of tomato plants exhibited high nematicidal activity against the free-living nematode Caenorhabditis elegans and the root-knot nematode Meloidogyne incognita. In a pot experiment, control efficiency of B. mycoides R2 on M. incognita was as high as 90.94%. The nematicidal compound was isolated and identified as styrene. The median lethal concentration of styrene against M. incognita was 4.55 g/ml (m/v). The volatile styrene caused avoidance and killed nematodes primarily by the olfactory neuron and G protein signal pathway. C. elegans detected styrene with the AWB neuron; the signal was then transmitted to the downstream G protein coupled receptors CHE-3, DOP-3, and STR-2. Then signal activated G protein GPA-3 and GPA-7. The signal was then transmitted to ion channels (CNGs channel and TRPV channel), causing calcium ion internal flow and a stress response towards the increased concentration of intracellular calcium. Styrene should be registered as a nematode repellent and biocontrol agent for protection of crops against root-knot nematode attack.

Luo H et al. (2024) J Lipid Res "Sphingolipid profiling reveals differential functions of sphingolipid biosynthesis isozymes of C. elegans."

Wu G, Xia Y, Dong MQ, Luo H, Zhao X, Wang ZD, Ma Y

[J Lipid Res, 2024]

Multiple isozymes are encoded in the C. elegans genome for the various sphingolipid biosynthesis reactions, but the contributions of individual isozymes are characterized only in part. We developed a simple but effective reversed-phase liquid chromatography-tandem mass spectrometry (RPLC-MS/MS) method that enables simultaneous identification and quantification of ceramides (Cer), glucosylceramides (GlcCer), and sphingomyelins (SM), three important classes of sphingolipids from the same MS run. Validating this sphingolipid profiling method, we show that nearly all 47 quantifiable sphingolipid species found in young adult worms were reduced upon RNA interference (RNAi) of sptl-1 or elo-5, which are required for synthesis of the id17:1 sphingoid base. We also confirm that HYL-1 and HYL-2, but not LAGR-1, constitute the major ceramide synthase activity with different preference for fatty acid substrates, and that CGT-3, but not CGT-1 and CGT-2, plays a major role in producing glucosylceramides. Deletion of sms-5 hardly affects SM levels. RNAi of sms-1, -2, and -3 all lower the abundance of sphingomyelins with an odd number of carbon atoms (mostly C21 and C23, with or without hydroxylation) in the N-acyl chain, and only sms-1 RNAi does not elevate sphingomyelins containing even-numbered N-acyl chains. This suggests that sphingolipids containing even-numbered N-acyl chains could be regulated separately, sometimes in opposite directions, with those containing odd-numbered N-acyls, presumably monomethyl branched chain fatty acyls. We also find that ceramide levels are kept in balance with those of glucosylceramides and sphingomyelins.