Expansion of Voltage-dependent Na+ Channel Gene Family in Early Tetrapods Coincided with the Emergence of Terrestriality and Increased Brain Complexity

Zakon, Harold H.; Jost, Manda C.; Lu, Ying

doi:10.1093/molbev/msq325

Cited by 48 publications

(50 citation statements)

References 52 publications

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“…It was suggested that expansion of Na V subtypes in vertebrates correlated with increased neuronal complexity (Zakon et al, 2011) and it is tempting to hypothesize that the same might be true for the expansions in Cnidaria. However, a functional approach is required for testing this hypothesis.…”

Section: Open Questions Challenges and Future Directionsmentioning

confidence: 99%

“…In the human genome there are 10 genes encoding Na V s (Na V 1.1-Na V 1.9 and Na X ). It is thought that in the common ancestor of vertebrates only one Na V 1 gene was present, which underwent two rounds of duplication in the basal vertebrate and further duplication and diversification in teleosts and tetrapods (Widmark et al, 2011;Zakon et al, 2011). As in the case of K V s discussed before, the finding of such a diversity of sodium channels in a sea anemone was highly unexpected (Gur Barzilai et al, 2012).…”

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confidence: 98%

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Evolution of voltage-gated ion channels at the emergence of Metazoa

Moran

Barzilai

Liebeskind

et al. 2015

Journal of Experimental Biology

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128

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Voltage-gated ion channels are large transmembrane proteins that enable the passage of ions through their pore across the cell membrane. These channels belong to one superfamily and carry pivotal roles such as the propagation of neuronal and muscular action potentials and the promotion of neurotransmitter secretion in synapses. In this review, we describe in detail the current state of knowledge regarding the evolution of these channels with a special emphasis on the metazoan lineage. We highlight the contribution of the genomic revolution to the understanding of ion channel evolution and for revealing that these channels appeared long before the appearance of the first animal. We also explain how the elucidation of channel selectivity properties and function in non-bilaterian animals such as cnidarians (sea anemones, corals, jellyfish and hydroids) can contribute to the study of channel evolution. Finally, we point to open questions and future directions in this field of research. KEY WORDS: Voltage-gated ion channels, Animal evolution, Ion selectivity Introduction: the superfamily of voltage-gated ion channelsThis review aims to cover and clarify the evolution and diversification of metazoan voltage-gated ion channels, particularly at the beginning of multicellularity in the lineage leading to Metazoa and at the emergence of nervous systems. Voltage-gated ion channels are imperative for neuronal signaling, muscle contraction and secretion, and are thought to play a critical role in the evolution of animals (Hille, 2001). Nonetheless, these channels are also found in prokaryotes and viruses, although their roles in these organisms are largely unknown (Martinac et al., 2008;Plugge et al., 2000). The superfamily of voltage-gated ion channels is characterized by the ability to rapidly respond to changes in membrane potential (hence 'voltage-gated'), which results in selective ion conductance. This ion channel superfamily includes voltage-gated potassium channels (K V s), voltage-gated calcium channels (Ca V s) and voltage-gated sodium channels (Na V s). Their α-subunits are composed of four domains (DI-IV), with each domain containing six transmembrane segments (S1-S6; Fig. 1) (Noda et al., 1984;Noda et al., 1986;Guy and Seetharamulu, 1986;Tanabe et al., 1987). Voltage-dependent activation is enabled by conserved positively charged residues at every third position in S4 (voltage sensor) of the four domains, which move outwards upon changes in membrane potential (Noda et al., 1984; Catterall, 1986;Guy and Seetharamulu, 1986), inducing a conformational change that results in opening of the channel pore (Armstrong and Bezanilla, 1974;Stühmer et al., 1989;Papazian et al., 1991;Yang et al., 1996). The pore is formed by the segments S5 and S6, and the selectivity to specific ions is enabled by the selectivity filter, which is composed of conserved residues, specific for the ion conducted by the channel, and these residues are situated at the pore-lining loops (p-loops) connecting S5 to S6 in the four domains ( ...

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Section: Open Questions Challenges and Future Directionsmentioning

confidence: 99%

mentioning

confidence: 98%

Evolution of voltage-gated ion channels at the emergence of Metazoa

Moran

Barzilai

Liebeskind

et al. 2015

Journal of Experimental Biology

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128

116

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“…13) (Hellsten et al, 2010;Zakon et al, 2011). Detailed description of the development of the methods in paper III can be found in the methods section ("Finding a gene in an unsequenced genome" and "Alter the expression level of a SCN2A ortholog").…”

Section: Resultsmentioning

confidence: 99%

“…The gene sequences for six Na v channels from X. tropicalis are partly known and can be retrieved at www.xenbase.org. (Gilchrist, 2012;Hellsten et al, 2010;Zakon et al, 2011) To explore the possibility to target specific Na v channel sequences in X. laevis using primers designed for X. tropicalis, tissues from X. laevis with known expression of different Na v channel genes (SCNA genes) were collected after the frogs were sacrificed (brain, heart, and skeletal muscles). Total mRNA was extracted from the tissues and cDNA created.…”

Section: Finding a Gene In An Unsequenced Genomementioning

confidence: 99%

The role of ion channels and intracellular metal ions in apoptosis of Xenopus oocytes

Englund¹

2014

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Apoptosis is one type of programmed cell death, important during tissue development and to maintain the tissue homeostasis. Apoptosis comprises a complex network of internal signaling pathways, and an important part of this signaling network is the action of voltage‐gated ion channels. The aim of this thesis was to explore the role of ion channels and the role of intracellular metal ions during apoptosis in Xenopus laevis oocytes. The reasons for using these oocytes are that they are large, robust, easy to handle, and easy to study electrophysiologically. Apoptosis was induced either chemically by incubation of the oocytes in staurosporine (STS) or mechanically by centrifugation of the oocytes. Ion currents were measured by a two‐electrode voltage clamp technique, intracellular ion concentrations were measured either directly by in‐house developed K+‐selective microelectrodes or indirectly by the electrophysiological technique, and apoptosis was measured by caspase‐3 activation. Paper I describes that the intracellular K+ concentration was reduced by about 30 % during STS‐induced apoptosis. However, this reduction was prevented by excessive expression of exogenous ion channels. Despite the magnitude of the intracellular K+ concentration, either normal or reduced level, the oocytes displayed normal signs of apoptosis, suggesting that the intracellular K+ reduction was not required for the apoptotic process. Because the intracellular K+ concentration was not critical for apoptosis we searched for other ion fluxes by exploring the electrophysiological properties of X. laevis oocytes. Paper II, describes a non‐inactivating Na+ current activated at positive membrane voltages that was upregulated by a factor of five during STS‐induced apoptosis. By preventing influx of Na+, the apoptotic signaling network involving capsase‐3 was prevented. To molecularly identify this voltage‐gated Na channel, the X. tropicalis genome and conserved regions of the human SCNA genes were used as a map. Paper III, shows that the voltage‐gated Na channel corresponds to the SCN2A gene ortholog and that supression of this SCN2A ortholog using miRNA prevented cell death. In conclusion, this thesis work demonstrated that a voltage‐gated Na channel is critical for the apoptotic process in X. laevis oocytes by increasing the intracellular Na+ concentration

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“…Na V s subsequently evolved from Ca V in apoikozoa, a phylum comprising animals and the closely related choanoflagellates (5). In tandem, the emergence of the sodium selectivity and fast (sub-millisecond) voltagedependent gating served as functional prerequisites for complex action potential firing and neuronal complexity (6). Further, five isoforms of sodium channel β-subunits have been identified, namely, β1, β2, β3, β4 and splice variant β1b (7)(8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Cross-kingdom auxiliary subunit modulation of a voltage-gated sodium channel

Molinarolo

Lee

Leisle

et al. 2018

Journal of Biological Chemistry

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Voltage-gated, sodium ion-selective channels (Na V ) generate electrical signals contributing to the upstroke of the action potential in animals. Na V s are also found in bacteria and are members of a larger family of tetrameric voltagegated channels that includes Ca V s, K V s, and Na V s. Prokaryotic Na V s likely emerged from a homotetrameric Ca 2+ -selective voltage-gated progenerator, and later developed Na + selectivity independently. The Na V signaling complex in eukaryotes contains auxiliary proteins, termed beta (β) subunits, which are potent modulators of the expression profiles and voltage-gated properties of the Na V pore, but it is unknown whether they can functionally interact with prokaryotic Na V channels. Herein, we report that the eukaryotic Na V β1-subunit isoform interacts with and enhances the surface expression as well as the voltage-dependent gating properties of the bacterial Na V , NaChBac in Xenopus oocytes. A phylogenetic analysis of the β-subunit gene family proteins confirms that these proteins appeared roughly 420 million years ago and that they have no clear homologues in bacterial phyla. However, a comparison between eukaryotic and bacterial Na V structures highlighted the presence of a conserved fold, which could support interactions with the β-subunit. Our the electrophysiological, biochemical, structural and bioinformatics results suggests that the prerequisites for β-subunit regulation are an evolutionarily stable and intrinsic property of some voltage-gated channels.

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Expansion of Voltage-dependent Na+ Channel Gene Family in Early Tetrapods Coincided with the Emergence of Terrestriality and Increased Brain Complexity

Cited by 48 publications

References 52 publications

Evolution of voltage-gated ion channels at the emergence of Metazoa

Evolution of voltage-gated ion channels at the emergence of Metazoa

The role of ion channels and intracellular metal ions in apoptosis of Xenopus oocytes

Cross-kingdom auxiliary subunit modulation of a voltage-gated sodium channel

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