Characterization of putative tachykinin peptides in Caenorhabditis elegans

Sakai, Naoko; Ohno, Hideto; Yoshida, Morikatsu; Iwamoto, Eri; Kurogi, Akito; Danfeng, Jiang; Sato, Takahiro; Miyazato, Minoru; Kojima, Masayasu; Kato, Jun; Ida, Takanori

doi:10.1016/j.bbrc.2021.04.063

Cited by 6 publications

(10 citation statements)

References 38 publications

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“…In addition, we deorphanized four novel C. elegans peptide GPCRs related to neuropeptide FF/SIFamide (NPR-35), tachykinin (TKR-2), NPY (NPR-12), and myoinhibitory peptide (SPRR-1) receptors (Data S9). The deorphanization of these receptors provides biochemical evidence for their predicted interactions with orthologs of neuropeptide FF/SIFamide (NLP-10), tachykinin (NLP-58), NPY (FLP-33) and myoinhibitory peptides (NLP-42) 42,57,60,102 , which further supports evolutionary conservation of these neuropeptide systems in nematodes.…”

Section: Characterization Of Ancestral Bilaterian Neuropeptide System...mentioning

confidence: 64%

“…In the last decades, reverse pharmacology has proven to be a successful approach for the deorphanization of GPCRs, by expressing receptors in heterologous cells and identifying their ligand(s) in a compound library 44 . This way, a broad range of peptide GPCRs have been deorphanized, including at least 138 receptors in humans, 36 in Drosophila melanogaster, and 29 in Caenorhabditis elegans 40,[45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61] . Nevertheless, many peptide GPCRs remain orphan receptors, hampering investigations into their functions 62 .…”

Section: Introductionmentioning

confidence: 99%

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System-wide mapping of neuropeptide-GPCR interactions inC. elegans

Beets¹,

Zels²,

Vandewyer³

et al. 2022

Preprint

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Neuropeptides are ancient, widespread signaling molecules that underpin almost all brain functions. They constitute a broad ligand-receptor network, mainly by binding to G protein-coupled receptors (GPCRs). However, the organization of the peptidergic network and roles of many neuropeptides remain elusive, as our insight into neuropeptide-receptor interactions is limited and many peptide GPCRs in animal models and humans are still orphan receptors. Here we report a genome-wide neuropeptide-GPCR interaction map in C. elegans. By reverse pharmacology screening of over 55,384 possible interactions, we identify 461 cognate peptide-GPCR couples that uncover a broad signaling network with specific and complex combinatorial interactions encoded across and within single peptidergic genes. These interactions provide insights into neuropeptide functions and evolution. Combining our dataset with phylogenetic analysis supports peptide-receptor co-evolution and conservation of at least 14 bilaterian peptidergic systems in C. elegans. This resource lays a foundation for system-wide analysis of the peptidergic network.

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Section: Characterization Of Ancestral Bilaterian Neuropeptide System...mentioning

confidence: 64%

Section: Introductionmentioning

confidence: 99%

System-wide mapping of neuropeptide-GPCR interactions inC. elegans

Beets¹,

Zels²,

Vandewyer³

et al. 2022

Preprint

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“…Nevertheless, the F-type Hdh-TK peptides had higher ligand activation in both Hdh-TKRL and Hdh-TKRS compared to Y-type Hdh-TK peptides, possibly explaining the strong selective pressure during the evolution process of TK precursor genes. Recently, in the nematode Caenorhabditis elegans , three TK-like peptides harboring a C-terminal LR/KGLRamide sequence showed potent agonist activities against the TKR ( 46 ). In addition, TKs, including SP, NKA, and NKB, from diverse phyla such as arthropods, mollusks, and mammals caused weak induction of the C. elegans TKR responses.…”

Section: Discussionmentioning

confidence: 99%

“…This phylogenic view coincides well with the previous results that the lophotrochozoan TKRs clustered in a distinct branch from the insect TKRs and their duplicated NTLRs ( 8 , 11 ). Recently identified TKRs, a deorphanized C. elegans TKR and predicted Asterias rubens TKRs ( 46 , 52 ), are positioned in different clades from the bilaterian TKR/NTLR superfamily, indicating their substantial diversifications during the evolution of the phyla Nematoda and Echinodermata. Further identification and characterization of TKRs in neglected phyla, such as echinoderms and cnidarians, can provide an opportunity for detailed exploration of the evolutionary processes of TKs and TKRs, and understanding of the possible pleiotropy of TK signaling and function.…”

Section: Discussionmentioning

confidence: 99%

“…The interaction of TK peptides with a C. elegans TKR also did not show evidence for the induction of intracellular cAMP accumulation. In contrast, the C. elegans TK peptides induced a robust increase in intracellular Ca 2+ in the TKR-expressing CHO cells ( 46 ). Nevertheless, most insect and vertebrate TKRs are activated by their endogenous TK peptides to stimulate the Gs/cAMP/PKA and Gq/Ca 2+ /PKC signaling pathways ( 1 , 18 , 53 – 55 ), suggesting that the signaling through bilaterian TKRs is diverse and complex.…”

Section: Discussionmentioning

confidence: 99%

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Multiple tachykinins and their receptors characterized in the gastropod mollusk Pacific abalone: Expression, signaling cascades, and potential role in regulating lipid metabolism

Lee

Kim²,

Park³

et al. 2022

Front. Endocrinol.

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Tachykinin (TK) families, including the first neuropeptide substance P, have been intensively explored in bilaterians. Knowledge of signaling of TK receptors (TKRs) has enabled the comprehension of diverse physiological processes. However, TK signaling systems are largely unknown in Lophotrochozoa. This study identified two TK precursors and two TKR isoforms in the Pacific abalone Haliotis discus hannai (Hdh), and characterized Hdh-TK signaling. Hdh-TK peptides harbored protostomian TK-specific FXGXRamide or unique YXGXRamide motifs at the C-termini. A phylogenetic analysis showed that lophotrochozoan TKRs, including Hdh-TKRs, form a monophyletic group distinct from arthropod TKRs and natalisin receptor groups. Although reporter assays demonstrated that all examined Hdh-TK peptides activate intracellular cAMP accumulation and Ca2+ mobilization in Hdh-TKR-expressing mammalian cells, Hdh-TK peptides with N-terminal aromatic residues and C-terminal FXGXRamide motifs were more active than shorter or less aromatic Hdh-TK peptides with a C-terminal YXGXRamide. In addition, we showed that ligand-stimulated Hdh-TKRs mediate ERK1/2 phosphorylation in HEK293 cells and that ERK1/2 phosphorylation is inhibited by PKA and PKC inhibitors. In three-dimensional in silico Hdh-TKR binding modeling, higher docking scores of Hdh-TK peptides were consistent with the lower EC50 values in the reporter assays. The transcripts for Hdh-TK precursors and Hdh-TKR were highly expressed in the neural ganglia, with lower expression levels in peripheral tissues. When abalone were starved for 3 weeks, Hdh-TK1 transcript levels, but not Hdh-TK2, were increased in the cerebral ganglia (CG), intestine, and hepatopancreas, contrasting with the decreased lipid content and transcript levels of sterol regulatory element-binding protein (SREBP). At 24 h post-injection in vivo, the lower dose of Hdh-TK1 mixture increased SREBP transcript levels in the CG and hepatopancreas and accumulative food consumption of abalone. Higher doses of Hdh-TK1 and Hdh-TK2 mixtures decreased the SREBP levels in the CG. When Hdh-TK2-specific siRNA was injected into abalone, intestinal SREBP levels were significantly increased, whereas administration of both Hdh-TK1 and Hdh-TK2 siRNA led to decreased SREBP expression in the CG. Collectively, our results demonstrate the first TK signaling system in gastropod mollusks and suggest a possible role for TK peptides in regulating lipid metabolism in the neural and peripheral tissues of abalone.

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