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Grill B et al. (2012) J Neurosci "RAE-1, a novel PHR binding protein, is required for axon termination and synapse formation in Caenorhabditis elegans."

Anderson M, Baker ST, Chen L, Quadroni M, Jin Y, Grill B, Bienvenut W, Tulgren ED, Garner CC

[

J Neurosci,

2012]

Previous studies in Caenorhabditis elegans showed that RPM-1 (Regulator of Presynaptic Morphology-1) regulates axon termination and synapse formation. To understand the mechanism of how rpm-1 functions, we have used mass spectrometry to identify RPM-1 binding proteins, and have identified RAE-1 (RNA Export protein-1) as an evolutionarily conserved binding partner. We define a RAE-1 binding region in RPM-1, and show that this binding interaction is conserved and also occurs between Rae1 and the human ortholog of RPM-1 called Pam (protein associated with Myc). rae-1 loss of function causes similar axon and synapse defects, and synergizes genetically with two other RPM-1 binding proteins, GLO-4 and FSN-1. Further, we show that RAE-1 colocalizes with RPM-1 in neurons, and that rae-1 functions downstream of rpm-1. These studies establish a novel postmitotic function for rae-1 in neuronal development.

Baker ST et al. (2017) J Biol Chem "Defining minimal binding regions in Regulator of Presynaptic Morphology 1 (RPM-1) using C. elegans neurons reveals differential signaling complexes."

Baker ST, Grill B

[

J Biol Chem,

2017]

The intracellular signaling protein RPM-1 is a conserved regulator of synapse formation and axon termination in C. elegans. RPM-1 functions in a ubiquitin ligase complex with the F-box protein FSN-1, and functions through the microtubule binding protein RAE-1. Using a structure-function approach and positive selection for transgenic C. elegans, we explored the biochemical relationship between RPM-1, FSN-1, and RAE-1. This led to the identification of two new domains in RPM-1 that are sufficient for binding to FSN-1, called FSN-1 binding domain 2 (FBD2) and FBD3. Furthermore, we map the RAE-1 binding domain (RBD) to a much smaller region of RPM-1. Point mutations in RPM-1 that reduce binding to RAE-1 did not affect FSN-1 binding, indicating that RPM-1 utilizes different biochemical mechanisms to bind these molecules. Analysis of RPM-1 protein complexes in the neurons of C. elegans elucidated two further discoveries. 1) FSN-1 binds to RAE-1, and this interaction is not mediated by RPM-1. 2) RPM-1 binding to FSN-1 and RAE-1 reduces FSN-1/RAE-1 complex formation. These results indicate that RPM-1 uses different mechanisms to recruit FSN-1 and RAE-1 into independent signaling complexes in neurons.

Grill, B. et al. (2011) International Worm Meeting "RAE-1 a novel PHR binding protein regulates axon termination and synapse formation."

Garner, C.C., Chen, L., Bienvenut, W., Baker, S.T., Jin, Y., Grill, B., Anderson, M., Tulgren, E.D.

[

International Worm Meeting,

2011]

Pam/Highwire/RPM-1 (PHR) proteins are conserved from C. elegans to mammals, and play a critical role in synapse formation, axon guidance and axon termination. In C. elegans, the Regulator of Presynaptic Morphology (RPM)-1 functions with FSN-1 to negatively regulate the DLK-1 MAP kinase pathway. RPM-1 also positively regulates a Rab GTPase pathway that includes: GLO-4 and GLO-1. To further understand the mechanism of how RPM-1 functions, we biochemically purified RPM-1, and used mass spectrometry to identify RPM-1 binding proteins. Here we report the identification of RNA Export protein (RAE)-1 (also called Nuclear Pore Protein (NPP)-17) as a novel RPM-1 binding protein. The biochemical interaction between RPM-1 and RAE-1 is evolutionarily conserved as it also occurs between Pam (the human PHR protein), and rat Rae1. A conserved domain in the PHR proteins is sufficient for binding to RAE-1, and point mutations were identified that reduce binding to RAE-1. Previous studies in yeast and mammals have shown that Rae1 functions as a cell cycle regulator, as a regulator of chromosome segregation, and as an mRNA export factor. While mammalian Rae1 and C. elegans RAE-1 are expressed in neurons, their postmitotic function remains unknown. To address the functional significance of RAE-1 binding to RPM-1, we performed a series of genetic experiments. Previous studies have shown that rpm-1 loss of function (lf) mutants have defects in axon termination in the mechanosensory neurons, and have defects in synapse formation in the motor neurons. rae-1(tm2784) mutants have similar axon termination defects to rpm-1 (lf) mutants, although they occur with lower penetrance. Double mutants of rae-1 and other RPM-1 binding proteins, such as fsn-1 and glo-4, have enhanced defects in axon termination. rae-1;fsn-1 and rae-1;glo-4 double mutants also have enhanced defects in synapse formation in the GABAergic motor neurons. rae-1;rpm-1 double mutants are not enhanced demonstrating that rae-1 functions in the same pathway as rpm-1. Transgenic expression of RPM-1 that is point mutated to reduce binding to RAE-1 does not rescue axon termination defects in rpm-1 (lf) mutants with the same efficacy as expression of wild-type RPM-1. These observations highlight the importance of RAE-1 and its interaction with RPM-1 for axon and synapse development.

Lundquist EA (2003) Curr Opin Neurobiol "Rac proteins and the control of axon development."

Lundquist EA

[

Curr Opin Neurobiol,

2003]

Rac GTPases and their effectors control cellular morphogenesis in a wide range of developmental contexts by regulating the structure and dynamics of the actin cytoskeleton. Although much is known about the biochemistry of Racs and Rae regulators, less is known about how Racs control cellular morphogenesis, including axon development, in vivo. Recent loss-of-function genetic studies using model organisms have shown that Racs and their effectors are required for multiple aspects of axon development, including axon outgrowth, axon guidance and axon branching. Interestingly, these studies have also revealed that Rac activity is required to prune spurious axons and branches. Analyses of Racs and their upstream and downstream effectors suggest that Rae signaling is complex. Different neurons utilize distinct combinations of upstream Rae regulators during axon development, possibly reflecting responses to different axon path-finding signals, and Racs use distinct downstream effectors to mediate different aspects of axon development, possibly reflecting differential regulation of the lamellipodial and filopodial growth-cone actin-cytoskeleton domains underlying axon developmental events.

Souza ACR et al. (2018) Genes (Basel) "Pathogenesis of the Candida parapsilosis Complex in the Model Host Caenorhabditis elegans."

Fuchs BB, Mylonakis E, Colombo AL, Alves VS, Souza ACR, Jayamani E

[

Genes (Basel),

2018]

Caenorhabditiselegans is a valuable tool as an infection model toward the study of Candida species. In this work, we endeavored to develop a C. elegans-Candidaparapsilosis infection model by using the fungi as a food source. Three species of the C. parapsilosis complex (C.parapsilosis (sensustricto), Candidaorthopsilosis and Candidametapsilosis) caused infection resulting in C. elegans killing. All three strains that comprised the complex significantly diminished the nematode lifespan, indicating the virulence of the pathogens against the host. The infection process included invasion of the intestine and vulva which resulted in organ protrusion and hyphae formation. Importantly, hyphae formation at the vulva opening was not previously reported in C. elegans-Candida infections. Fungal infected worms in the liquid assay were susceptible to fluconazole and caspofungin and could be found to mount an immune response mediated through increased expression of cnc-4, cnc-7, and fipr-22/23. Overall, the C. elegans-C. parapsilosis infection model can be used to model C. parapsilosis host-pathogen interactions.

Fourie R et al. (2021) Front Cell Infect Microbiol "Candida albicans SET3 Plays a Role in Early Biofilm Formation, Interaction With Pseudomonas aeruginosa and Virulence in Caenorhabditis elegans."

Gcilitshana O, Fourie R, Albertyn J, Sebolai O, Pohl CH

[

Front Cell Infect Microbiol,

2021]

The yeast Candida albicans exhibits multiple morphologies dependent on environmental cues. Candida albicans biofilms are frequently polymicrobial, enabling interspecies interaction through proximity and contact. The interaction between C. albicans and the bacterium, Pseudomonas aeruginosa, is antagonistic in vitro, with P. aeruginosa repressing the yeast-to-hyphal switch in C. albicans. Previous transcriptional analysis of C. albicans in polymicrobial biofilms with P. aeruginosa revealed upregulation of genes involved in regulation of morphology and biofilm formation, including SET3, a component of the Set3/Hos2 histone deacetylase complex (Set3C). This prompted the question regarding the involvement of SET3 in the interaction between C. albicans and P. aeruginosa, both in vitro and in vivo. We found that SET3 may influence early biofilm formation by C. albicans and the interaction between C. albicans and P. aeruginosa. In addition, although deletion of SET3 did not alter the morphology of C. albicans in the presence of P. aeruginosa, it did cause a reduction in virulence in a Caenorhabditis elegans infection model, even in the presence of P. aeruginosa.

Coomansingh-Springer C et al. (2019) Heliyon "Internal parasitic burdens in brown rats (Rattus norvegicus) from Grenada, West Indies."

Vishakha V, Acuna AM, Sharma RN, Coomansingh-Springer C, Armstrong E

[

Heliyon,

2019]

This study identified the endoparasites in Brown rat (Rattus norvegicus) during May to July 2017 in Grenada, West Indies. A total of 162 rats, 76 females and 86 males were trapped from St. George and St. David parishes in Grenada. The collected fecal samples were examined for parasitic eggs and/or oocysts using simple fecal flotation technique. Adult parasites found in the intestinal tract were examined for identification. The overall prevalence of intestinal parasites among rats was 79 %. Ten helminth species were recovered, several of which were reported for the first time in rodents in Grenada. The internal parasites consist of seven nematodes (Angiostrongylus spp., Nippostrongylus braziliensis, Heterakis spumosa, Strongyloides ratti, Aspiculuris tetraptera, Syphacia spp. and Protospirura spp.), one cestode (Hymenolepsis diminuta), one acanthocephalan (Moniliformis moniliformis) and one protozoa species (Eimeria spp.). The most prevalent zoonotic species were Angiostrongylus spp. (35.2%), Hymenolepsis diminuta (7.4%) and Moniliformis moniliformis (3.1%). Several nonzoonotic endoparasites; which included Nippostrongylus braziliensis (50.6%), Heterakis spumosa (15.4%), Strongyloides ratti (43.2%), Aspiculuris tetraptera (2.5%), Syphacia spp. (1.9%), Protospirura spp. (1.2%) and Eimeria spp. (4.7%) were also identified. The most prevalent parasites were Nippostrongylus brasiliensis (50.6%), Strongyloides ratti (43.2%) and Angiostrongylus spp. (35.2%). Co-infections occurred with up to six species per rat showing different combinations of parasitic infections.

Zhu Q et al. (2020) Oxid Med Cell Longev "A Dihydroflavonoid Naringin Extends the Lifespan of C. elegans and Delays the Progression of Aging-Related Diseases in PD/AD Models via DAF-16."

Zhou XG, Wu GS, Chen JN, Zhu Q, Qu Y, Luo HR

[

Oxid Med Cell Longev,

2020]

Naringin is a dihydroflavonoid, which is rich in several plant species used for herbal medicine. It has a wide range of biological activities, including antineoplastic, anti-inflammatory, antiphotoaging, and antioxidative activities. So it would be interesting to know if naringin has an effect on aging and aging-related diseases. We examined the effect of naringin on the aging of Caenorhabditis elegans (C. elegans). Our results showed that naringin could extend the lifespan of C. elegans. Moreover, naringin could also increase the thermal and oxidative stress tolerance, reduce the accumulation of lipofuscin, and delay the progress of aging-related diseases in C. elegans models of AD and PD. Naringin could not significantly extend the lifespan of long-lived mutants from genes in insulin/IGF-1 signaling (IIS) and nutrient-sensing pathways, such as daf-2, akt-2, akt-1, eat-2, sir-2.1, and rsks-1. Naringin treatment prolonged the lifespan of long-lived glp-1 mutants, which have decreased reproductive stem cells. Naringin could not extend the lifespan of a null mutant of the fox-head transcription factor DAF-16. Moreover, naringin could increase the mRNA expression of genes regulated by daf-16 and itself. In conclusion, we show that a natural product naringin could extend the lifespan of C. elegans and delay the progression of aging-related diseases in C. elegans models via DAF-16.

Wu CJ et al. (2019) Appl Environ Microbiol "Genotypic and Phenotypic Characteristics of Aeromonas Isolates from Fish and Patients in Tainan City."

Su YC, Lee NY, Chen PL, Ko WC, Li CW, Chen YW, Li MC, Wu CJ, Shu CY, Su SL, Lin YT

[

Appl Environ Microbiol,

2019]

The present study aimed to isolate Aeromonas from fish sold in the markets as well as in sushi and seafood shops and compare their virulence factors and antimicrobial characteristics with those of clinical isolates. Among the 128 fish isolates and 47 clinical isolates, A. caviae, A. dhakensis, and A. veronii were the principal species. A. dhakensis isolates carried at least 5 virulence genes, more than other Aeromonas species. The predominant genotype of virulence genes was hlyA/lip/alt/col/el in both A. dhakensis and A. hydrophila isolates, alt/col/ela in A. caviae isolates, and act in A. veronii isolates. A. dhakensis, A. hydrophila, and A. veronii isolates more often exhibited hemolytic and proteolytic activity and showed greater virulence than A. caviae in Caenorhabditis elegans and the C2C12 cell line. However, the link between the genotypes and phenotypes of the studied virulence genes in Aeromonas species is not evident. Among the four major clinical Aeromonas species, nearly all (99.0%) A. dhakensis, A. hydrophila, and A. veronii isolates harbored blaCphA, which encodes a carbapenemase, but only a minority (6.7%, 7/104) were nonsusceptible to carbapenem. Regarding AmpC -lactamase genes, blaAQU-1 was exclusively found in A. dhakensis isolates and blaMOX3 only in A. caviae isolates, but only 7.6% (6) of the 79 Aeromonas isolates carrying blaAQU-1 or blaMOX3 exhibited a cefotaxime resistance phenotype. In conclusion, fish Aeromonas isolates carry a variety of combinations of virulence and B-lactamase resistance genes and exhibit virulence phenotypes and antimicrobial resistance profiles similar to those of clinical isolates.IMPORTANCEAeromonas species can cause severe infections in immunocompromised individuals upon exposure to virulent pathogens in the environment, but the characteristics of environmental Aeromonas species remain unclear. Our study showed several pathogenic Aeromonas species possessing virulence traits and antimicrobial resistance similar to those of Aeromonas isolates causing clinical diseases were present in fish intended for human consumption in Tainan City.

Hariri S et al. (2023) MicroPubl Biol "53bp1 mutation enhances brca1 and bard1 embryonic lethality in C. elegans."

Li Q, Hariri S, Engebrecht J

[

MicroPubl Biol,

2023]

In mice, mutation of brca1 results in embryonic lethality, which is partially suppressed by 53bp1 mutation. In contrast, mutation of the C. elegans BRCA1 ortholog, brc-1 , or its binding partner, brd-1 , lead to only mild embryonic lethality. We show that in C. elegans , brc-1 and brd-1 embryonic lethality is enhanced when 53bp1 ortholog, hsr-9 , is also mutated. This is not a consequence of activating polq-1 -dependent microhomology-mediated end joining, as polq-1 mutation does not suppress embryonic lethality of hsr-9 ; brc-1 mutants. Together, these results suggest that BRC-1 - BRD-1 and HSR-9 function in parallel pathways and do not act antagonistically as in mammals.

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