Characterization of a new type of neuronal 5-HT G- protein coupled receptor in the cestode nervous system

Cestodes are platyhelminth parasites with a wide range of hosts that cause neglected diseases. Neurotransmitter signaling is of critical importance for these parasites which lack circulatory, respiratory and digestive systems. For example, serotonin (5-HT) and serotonergic G-protein coupled receptor...

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Autores principales: Federico Camicia, Hugo R. Vaca, Sang-Kyu Park, Augusto E. Bivona, Ariel Naidich, Matias Preza, Uriel Koziol, Ana M. Celentano, Jonathan S. Marchant, Mara C. Rosenzvit
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Publicado: Public Library of Science (PLoS) 2021
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spelling oai:doaj.org-article:29883624c26c4568993ab765dc15c4c02021-11-18T08:14:32ZCharacterization of a new type of neuronal 5-HT G- protein coupled receptor in the cestode nervous system1932-6203https://doaj.org/article/29883624c26c4568993ab765dc15c4c02021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584985/?tool=EBIhttps://doaj.org/toc/1932-6203Cestodes are platyhelminth parasites with a wide range of hosts that cause neglected diseases. Neurotransmitter signaling is of critical importance for these parasites which lack circulatory, respiratory and digestive systems. For example, serotonin (5-HT) and serotonergic G-protein coupled receptors (5-HT GPCRs) play major roles in cestode motility, development and reproduction. In previous work, we deorphanized a group of 5-HT7 type GPCRs from cestodes. However, little is known about another type of 5-HT GPCR, the 5-HT1 clade, which has been studied in several invertebrate phyla but not in platyhelminthes. Three putative 5-HT GPCRs from Echinococcus canadensis, Mesocestoides vogae (syn. M. corti) and Hymenolepis microstoma were cloned, sequenced and bioinformatically analyzed. Evidence grouped these new sequences within the 5-HT1 clade of GPCRs but differences in highly conserved GPCR motifs were observed. Transcriptomic analysis, heterologous expression and immunolocalization studies were performed to characterize the E. canadensis receptor, called Eca-5-HT1a. Functional heterologous expression studies showed that Eca-5-HT1a is highly specific for serotonin. 5-Methoxytryptamine and α-methylserotonin, both known 5-HT GPCR agonists, give stimulatory responses whereas methysergide, a known 5-HT GPCR ligand, give an antagonist response in Eca-5-HT1a. Mutants obtained by the substitution of key predicted residues resulted in severe impairment of receptor activity, confirming that indeed, these residues have important roles in receptor function. Immunolocalization studies on the protoscolex stage from E. canadensis, showed that Eca-5-HT1a is localized in branched fibers which correspond to the nervous system of the parasite. The patterns of immunoreactive fibers for Eca-5-HT1a and for serotonin were intimately intertwined but not identical, suggesting that they are two separate groups of fibers. These data provide the first functional, pharmacological and localization report of a serotonergic receptor that putatively belongs to the 5-HT1 type of GPCRs in cestodes. The serotonergic GPCR characterized here may represent a new target for antiparasitic intervention.Federico CamiciaHugo R. VacaSang-Kyu ParkAugusto E. BivonaAriel NaidichMatias PrezaUriel KoziolAna M. CelentanoJonathan S. MarchantMara C. RosenzvitPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Federico Camicia
Hugo R. Vaca
Sang-Kyu Park
Augusto E. Bivona
Ariel Naidich
Matias Preza
Uriel Koziol
Ana M. Celentano
Jonathan S. Marchant
Mara C. Rosenzvit
Characterization of a new type of neuronal 5-HT G- protein coupled receptor in the cestode nervous system
description Cestodes are platyhelminth parasites with a wide range of hosts that cause neglected diseases. Neurotransmitter signaling is of critical importance for these parasites which lack circulatory, respiratory and digestive systems. For example, serotonin (5-HT) and serotonergic G-protein coupled receptors (5-HT GPCRs) play major roles in cestode motility, development and reproduction. In previous work, we deorphanized a group of 5-HT7 type GPCRs from cestodes. However, little is known about another type of 5-HT GPCR, the 5-HT1 clade, which has been studied in several invertebrate phyla but not in platyhelminthes. Three putative 5-HT GPCRs from Echinococcus canadensis, Mesocestoides vogae (syn. M. corti) and Hymenolepis microstoma were cloned, sequenced and bioinformatically analyzed. Evidence grouped these new sequences within the 5-HT1 clade of GPCRs but differences in highly conserved GPCR motifs were observed. Transcriptomic analysis, heterologous expression and immunolocalization studies were performed to characterize the E. canadensis receptor, called Eca-5-HT1a. Functional heterologous expression studies showed that Eca-5-HT1a is highly specific for serotonin. 5-Methoxytryptamine and α-methylserotonin, both known 5-HT GPCR agonists, give stimulatory responses whereas methysergide, a known 5-HT GPCR ligand, give an antagonist response in Eca-5-HT1a. Mutants obtained by the substitution of key predicted residues resulted in severe impairment of receptor activity, confirming that indeed, these residues have important roles in receptor function. Immunolocalization studies on the protoscolex stage from E. canadensis, showed that Eca-5-HT1a is localized in branched fibers which correspond to the nervous system of the parasite. The patterns of immunoreactive fibers for Eca-5-HT1a and for serotonin were intimately intertwined but not identical, suggesting that they are two separate groups of fibers. These data provide the first functional, pharmacological and localization report of a serotonergic receptor that putatively belongs to the 5-HT1 type of GPCRs in cestodes. The serotonergic GPCR characterized here may represent a new target for antiparasitic intervention.
format article
author Federico Camicia
Hugo R. Vaca
Sang-Kyu Park
Augusto E. Bivona
Ariel Naidich
Matias Preza
Uriel Koziol
Ana M. Celentano
Jonathan S. Marchant
Mara C. Rosenzvit
author_facet Federico Camicia
Hugo R. Vaca
Sang-Kyu Park
Augusto E. Bivona
Ariel Naidich
Matias Preza
Uriel Koziol
Ana M. Celentano
Jonathan S. Marchant
Mara C. Rosenzvit
author_sort Federico Camicia
title Characterization of a new type of neuronal 5-HT G- protein coupled receptor in the cestode nervous system
title_short Characterization of a new type of neuronal 5-HT G- protein coupled receptor in the cestode nervous system
title_full Characterization of a new type of neuronal 5-HT G- protein coupled receptor in the cestode nervous system
title_fullStr Characterization of a new type of neuronal 5-HT G- protein coupled receptor in the cestode nervous system
title_full_unstemmed Characterization of a new type of neuronal 5-HT G- protein coupled receptor in the cestode nervous system
title_sort characterization of a new type of neuronal 5-ht g- protein coupled receptor in the cestode nervous system
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/29883624c26c4568993ab765dc15c4c0
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