The Conserved G-Protein Coupled Receptor FSHR-1 Regulates Protective Host Responses to Infection and Oxidative Stress

Miller, Elizabeth V.; Grandi, Leah N.; Giannini, Jennifer A.; Robinson, Joseph D.; Powell, Jennifer R.

doi:10.1371/journal.pone.0137403

Cited by 35 publications

(60 citation statements)

References 43 publications

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“…The G-protein coupled receptor (GPCR) FSHR-1 has been implicated in the survival of heavy metal and oxidative stress, as well as the innate immune response. Worms containing null mutations in fshr-1 have wild-type longevity under normal growth conditions, but have increased sensitivity to oxidative, heavy metal, and pathogen stresses [ 15 , 17 ] . Surprisingly these mutant worms are resistant to 2 °C cold shock (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Interestingly, the G-protein coupled receptor FSHR-1 is required for the survival of exogenous oxidative stress and pathogen stress (infection). Infected fshr-1 null mutants fail to activate this ROS detoxification program, suggesting that FSHR-1 might be one link between the repair and recovery of oxidative stress and pathogen stress [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Long-term recovery from acute cold shock in Caenorhabditis elegans

Robinson¹,

Powell²

2016

BMC Cell Biol

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BackgroundAnimals are exposed to a wide range of environmental stresses that can cause potentially fatal cellular damage. The ability to survive the period of stress as well as to repair any damage incurred is essential for fitness. Exposure to 2 °C for 24 h or longer is rapidly fatal to the nematode Caenorhabditis elegans, but the process of recovery from a shorter, initially non-lethal, cold shock is poorly understood.ResultsWe report that cold shock of less than 12-hour duration does not initially kill C. elegans, but these worms experience a progression of devastating phenotypes over the next 96 h that correlate with their eventual fate: successful recovery from the cold shock and survival, or failure to recover and death. Cold-shocked worms experience a marked loss of pigmentation, decrease in the size of their intestine and gonads, and disruption to the vulva. Those worms who will successfully recover from the cold shock regain their pigmentation and much of the integrity of their intestine and gonads. Those who will die do so with a distinct phenotype from worms dying during or immediately following cold shock, suggesting independent mechanisms. Worms lacking the G-protein coupled receptor FSHR-1 are resistant to acute death from longer cold shocks, and are more successful in their recovery from shorter sub-lethal cold shocks.ConclusionsWe have defined two distinct phases of death associated with cold shock and described a progression of phenotypes that accompanies the course of recovery from that cold shock. The G-protein coupled receptor FSHR-1 antagonizes these novel processes of damage and recovery.Electronic supplementary materialThe online version of this article (doi:10.1186/s12860-015-0079-z) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Long-term recovery from acute cold shock in Caenorhabditis elegans

Robinson¹,

Powell²

2016

BMC Cell Biol

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“…Like many invertebrates, C. elegans has a homolog of vertebrate glycoprotein receptors, which include TSH receptors. The ortholog FSHR-1 is involved in innate immunity, stress responses, and germline fertility (69)(70)(71). The C. elegans genome also encodes two genes, flr-2 and T23B12.8, for α and β glycoprotein subunits (72,73).…”

Section: Discussionmentioning

confidence: 99%

Evolutionarily conserved TRH neuropeptide pathway regulates growth in Caenorhabditis elegans

Sinay

Mirabeau

Depuydt

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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In vertebrates thyrotropin-releasing hormone (TRH) is a highly conserved neuropeptide that exerts the hormonal control of thyroidstimulating hormone (TSH) levels as well as neuromodulatory functions. However, a functional equivalent in protostomian animals remains unknown, although TRH receptors are conserved in proto-and deuterostomians. Here we identify a TRH-like neuropeptide precursor in Caenorhabditis elegans that belongs to a bilaterian family of TRH precursors. Using CRISPR/Cas9 and RNAi reverse genetics, we show that TRH-like neuropeptides, through the activation of their receptor TRHR-1, promote growth in C. elegans. TRH-like peptides from pharyngeal motor neurons are required for normal body size, and knockdown of their receptor in pharyngeal muscle cells reduces growth. Mutants deficient for TRH signaling have no defects in pharyngeal pumping or isthmus peristalsis rates, but their growth defect depends on the bacterial diet. In addition to the decrease in growth, trh-1 mutants have a reduced number of offspring. Our study suggests that TRH is an evolutionarily ancient neuropeptide, having its origin before the divergence of protostomes and deuterostomes, and may ancestrally have been involved in the control of postembryonic growth and reproduction.thyrotropin-releasing hormone | C. elegans | neuropeptide | molecular evolution | growth regulation A fter Harris's initial proposal on the hypothalamic control of pituitary secretion (1), it took almost two decades to identify the first hypophysiotropic molecule. In 1969 the groups of Schally and Guillemin isolated the tripeptide pQHP-NH 2 (2, 3), named "thyrotropin-releasing hormone" (TRH). The sequence of TRH is fully conserved across all vertebrates, indicating that strong evolutionary pressure has acted to preserve its structure (4). In all vertebrate phyla TRH is synthesized from a larger precursor protein (preproTRH) that contains five to eight copies of the TRH sequence (4). Following the explosion of genome and transcriptome sequence data, preproTRH was identified in chordate species lacking a bona fide pituitary, e.g., cephalochordates (5), and in the genomes of more ancient deuterostomes, including echinoderms (6, 7). In contrast to vertebrate (pQHP-NH 2 ) and chordate (pQSP-NH 2 ) tripeptide TRHs, most predicted echinoderm TRHs are tetrapeptidesLike vertebrate TRH, they are small peptides with an N-terminal pyroglutamate, a C-terminal amide (-NH 2 ) group, and amino acids with aromatic or cyclic side chains at the second and third positions. TRH therefore is widely distributed throughout the deuterostomian lineage of the Animal Kingdom, suggesting an ancient origin for this neuropeptide hormone.In mammals, hypothalamic TRH is the prime regulator of the set point of thyroid-stimulating hormone (TSH) synthesis and secretion by the anterior pituitary thyrotrophs (9). TSH secretion stimulates the thyroid gland to produce the thyroid hormones (THs) thyroxine (T 4 ) and triiodothyronine (T 3 ). The hypothalamus-pituitary-thyroid (HPT) axis is essentia...

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“…It has been suggested that microbial infections induce oxidative stress in C. elegans (Bolm et al, 2004;Miller et al, 2015;Sem and Rhen, 2012). We therefore treated worms with paraquat that is commonly used as an oxidative stress inducer (Senchuk et al, 2017).…”

Section: Endotube Dysfunction Correlates With Impaired Oxidative and mentioning

confidence: 99%

The intestinal intermediate filament network responds to and protects against microbial insults and toxins

et al. 2019

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The enrichment of intermediate filaments in the apical cytoplasm of intestinal cells is evolutionarily conserved, forming a sheath that is anchored to apical junctions and positioned below the microvillar brush border, which suggests a protective intracellular barrier function. To test this, we used Caenorhabditis elegans, the intestinal cells of which are endowed with a particularly dense intermediate filament-rich layer that is referred to as the endotube. We found alterations in endotube structure and intermediate filament expression upon infection with nematicidal B. thuringiensis or treatment with its major pore-forming toxin crystal protein Cry5B. Endotube impairment due to defined genetic mutations of intermediate filaments and their regulators results in increased Cry5B sensitivity as evidenced by elevated larval arrest, prolonged time of larval development and reduced survival. Phenotype severity reflects the extent of endotube alterations and correlates with reduced rescue upon toxin removal. The results provide in vivo evidence for a major protective role of a properly configured intermediate filament network as an intracellular barrier in intestinal cells. This notion is further supported by increased sensitivity of endotube mutants to oxidative and osmotic stress.

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The Conserved G-Protein Coupled Receptor FSHR-1 Regulates Protective Host Responses to Infection and Oxidative Stress

Cited by 35 publications

References 43 publications

Long-term recovery from acute cold shock in Caenorhabditis elegans

Long-term recovery from acute cold shock in Caenorhabditis elegans

Evolutionarily conserved TRH neuropeptide pathway regulates growth in Caenorhabditis elegans

The intestinal intermediate filament network responds to and protects against microbial insults and toxins

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