A Peptide-gated Ion Channel from the Freshwater Polyp Hydra

Golubovic, Andjelko; Kuhn, Anne; Williamson, Michael; Kalbacher, Hubert; Holstein, Thomas W.; Grimmelikhuijzen, Cornelis J.P.; Gründer, Stefan

doi:10.1074/jbc.m706849200

Cited by 97 publications

(143 citation statements)

References 27 publications

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“…Following the discovery of FaNaC, the first identified ligand-gated ion channel, scientists successively found other peptide ligand-gated channel members in the ENaC/DEG superfamily, such as HyNaC (22). New activation modes of well-known channels in response to small molecular ligands have also been established, including ASICs being activated by GMQ (6,54) and ENaC being activated by S3969 (5).…”

Section: Discussionmentioning

confidence: 99%

“…FaNaC is the first discovered peptide-gated ion channel identified in the ENaC/ DEG superfamily. Cloned from the freshwater Polyp Hydra, HyNaC is another ancient peptide-gated ion channel, activated by Hydra-RFamides (22). The existence of the peptide-gated channels in both mollusks and coelenterates suggests that an RFamide-gated channel already exists in a common ancestor of mollusks and coelenterates (16).…”

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Exploration of the Peptide Recognition of an Amiloride-sensitive FMRFamide Peptide-gated Sodium Channel

Niu

Yang

Liu

et al. 2016

Journal of Biological Chemistry

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FMRFamide (Phe-Met-Arg-Phe-NH 2 )-activated sodium channel (FaNaC) is an amiloride-sensitive sodium channel activated by endogenous tetrapeptide in invertebrates, and belongs to the epithelial sodium channel/degenerin (ENaC/DEG) superfamily. The ENaC/DEG superfamily differs markedly in its means of activation, such as spontaneously opening or gating by mechanical stimuli or tissue acidosis. Recently, it has been observed that a number of ENaC/DEG channels can be activated by small molecules or peptides, indicating that the ligand-gating may be an important feature of this superfamily. The peptide ligand control of the channel gating might be an ancient ligand-gating feature in this superfamily. Therefore, studying the peptide recognition of FaNaC channels would advance our understanding of the ligand-gating properties of this superfamily of ion channels. Here we demonstrate that Tyr-131, Asn-134, Asp-154, and Ile-160, located in the putative upper finger domain of Helix aspersa FaNaC (HaFaNaC) channels, are key residues for peptide recognition of this ion channel. Two HaFaNaC specificinsertion motifs among the ENaC/DEG superfamily, residing at the putative ␣4-␣5 linker of the upper thumb domain and the ␣6-␣7 linker of the upper knuckle domain, are also essential for the peptide recognition of HaFaNaC channels. Chemical modifications and double mutant cycle analysis further indicated that those two specific inserts and key residues in the upper finger domain together participate in peptide recognition of HaFaNaC channels. This ligand recognition site is distinct from that of acid-sensing ion channels (ASICs) by a longer distance between the recognition site and the channel gate, carrying useful information about the ligand gating and the evolution of the trimeric ENaC/DEG superfamily of ion channels.The epithelial sodium channel/Degenerin (ENaC/DEG) 4 superfamily, cloned in the early 1990s, is nonvoltage-gated, amiloride-sensitive, and sodium-selective ion channels, including ASIC, ENaC, DEG, FaNaC, bile acid-sensitive ion channel (BASIC), and pickpocket (PPK) channels, etc. (1, 2). ENaC/DEG ion channels are implicated in many physiological and pathological functions such as synaptic plasticity, learning and memory, emotion regulation, neurodegenerative diseases, epileptic seizures, pain sensation, mechano-sensation, blood pressure regulation, and cystic fibrosis (1-3), which makes them potential drug targets for those disorders. The members of the ENaC/ DEG superfamily differ markedly by means of activation. For example, DEG channels are mechano-sensitive; ENaC channels open spontaneously; ASIC channels are capable of sensing tissue acidosis, while FaNaC is activated by RFamide peptides, etc. (4). Recently, great advances have been made in the exploration of the activation mechanism of this superfamily. For example, it is now known that ENaC, ASIC3, BASIC, and ASIC1a channels can be activated by the small molecules S3969 (5), GMQ (6), bile acid (7), and peptide toxin (8, 9) respectively. These new findings sugge...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Exploration of the Peptide Recognition of an Amiloride-sensitive FMRFamide Peptide-gated Sodium Channel

Niu

Yang

Liu

et al. 2016

Journal of Biological Chemistry

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“…Finally, a novel ion channel, directly gated by the neuropeptides Hydra-RFamides I and II, was recently cloned from Hydra and found expressed in epitheliomuscular cells at the base of the tentacles (Golubovic et al, 2007;Durrnagel et al, 2010). Homology searches show that this channel relates to members of the DEG/ EnaC gene family, that includes the only peptide gated-ionotropic receptor known to date, FaNaC from snails.…”

Section: Classical Neurotransmitters In Hydra: or Absence Of Evidencmentioning

confidence: 99%

Coordinated modulation of cellular signaling through ligand-gated ion channels in Hydra vulgaris (Cnidaria, Hydrozoa)

Pierobon

2012

Int. J. Dev. Biol.

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Cnidarians lack well developed organs, but they have evolved the molecular and cellular components needed to assemble a nervous system. The apparent 'simplicity' of the cnidarian nervous net does not occur at the cellular level, but rather in the organisation of conducting systems. Cnidarian neurons are in fact electrically excitable, show the typical extended morphology and are connected by chemical synapses or gap junctions. They have been regarded as peptidergic, given the wealth of neuropeptides generally distributed along neurites and in cell bodies, supporting the hypothesis of a modulatory role in neurotransmission. However, the presence of clear-cored, as well as dense-cored synaptic vesicles in cnidarian neurons suggests both fast and slow synaptic transmission mechanisms. In fact, biochemical and functional evidence indicates that classical neurotransmitters and their metabolic partners are present in cnidarian tissues, where they are involved in coordinating motility and behavior. We have identified and characterized in Hydra tissues receptors to the inhibitory and excitatory amino acid neurotransmitters, GABA, glycine and NMDA, that are similar to mammalian ionotropic receptors in terms of their biochemical and pharmacological properties. These receptors appear to regulate pacemaker activities and their physiological correlates; in the live animal, they also affect feeding behavior, namely the duration and termination of the response elicited by reduced glutathione, with opposite actions of GABA and glycine or NMDA, respectively. These results suggest that modulation of cellular signaling through ligand-gated-ion channels is an ancient characteristic in the animal kingdom, and that the pharmacological properties of these receptors have been highly conserved during evolution.

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“…In 2007, four new ion channel subunits from Hydra were cloned that belong to the degenerin/epithelial Na + channel (DEG/ENaC) gene family (Golubovic et al, 2007). As DEG/ENaCs usually are selective Na + channels, the novel subunits were named Hydra Na + channels: HyNaC1-HyNaC4.…”

Section: Cloning Of a Peptide-gated Ion Channel From Hydra Magnipapilmentioning

confidence: 99%

Peptide-gated ion channels and the simple nervous system of Hydra

Gründer

Assmann

2015

Journal of Experimental Biology

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Neurons either use electrical or chemical synapses to communicate with each other. Transmitters at chemical synapses are either small molecules or neuropeptides. After binding to their receptors, transmitters elicit postsynaptic potentials, which can either be fast and transient or slow and longer lasting, depending on the type of receptor. Fast transient potentials are mediated by ionotropic receptors and slow long-lasting potentials by metabotropic receptors. Transmitters and receptors are well studied for animals with a complex nervous system such as vertebrates and insects, but much less is known for animals with a simple nervous system like Cnidaria. As cnidarians arose early in animal evolution, nervous systems might have first evolved within this group and the study of neurotransmission in cnidarians might reveal an ancient mechanism of neuronal communication. The simple nervous system of the cnidarian Hydra extensively uses neuropeptides and, recently, we cloned and functionally characterized an ion channel that is directly activated by neuropeptides of the Hydra nervous system. These results demonstrate the existence of peptide-gated ion channels in Hydra, suggesting they mediate fast transmission in its nervous system. As related channels are also present in the genomes of the cnidarian Nematostella, of placozoans and of ctenophores, it should be considered that the early nervous systems of cnidarians and ctenophores have co-opted neuropeptides for fast transmission at chemical synapses.

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A Peptide-gated Ion Channel from the Freshwater Polyp Hydra

Cited by 97 publications

References 27 publications

Exploration of the Peptide Recognition of an Amiloride-sensitive FMRFamide Peptide-gated Sodium Channel

Exploration of the Peptide Recognition of an Amiloride-sensitive FMRFamide Peptide-gated Sodium Channel

Coordinated modulation of cellular signaling through ligand-gated ion channels in Hydra vulgaris (Cnidaria, Hydrozoa)

Peptide-gated ion channels and the simple nervous system of Hydra

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