Voltage-Gated Calcium Channels in Invertebrates

Senatore, Adriano; Spafford, J. David

doi:10.1007/978-3-031-08881-0_6

Cited by 5 publications

(8 citation statements)

References 311 publications

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“…, Ciona intestinalis and Styela clava ) and cephalochordates ( Branchiostoma belcheri ) diverged. Consistent with previous reports, the monophyletic nature of Ca V 2 channels in cnidarians and platyhelminthes indicates that independent duplication likely occurred in these phyla giving rise to Ca V 2a, Ca V 2b, and Ca V 2c in cnidarians, and Ca V 2A and Ca V 2B in platyhelminthes [2, 4, 36].…”

Section: Resultssupporting

confidence: 90%

“…The three vertebrate Ca V 2 channel isotypes, P/Q-type (Ca V 2.1), N-type (Ca V 2.2), and R-type (Ca V 2.3) form a monophyletic clade reflecting their emergence through more recent gene/genome duplication events that occurred within the phylum Chordata, after tunicates (e.g., Ciona intestinalis and Styela clava) and cephalochordates (Branchiostoma belcheri) diverged. Consistent with previous reports, the monophyletic nature of Ca V 2 channels in cnidarians and platyhelminthes indicates that independent duplication likely occurred in these phyla giving rise to Ca V 2a, Ca V 2b, and Ca V 2c in cnidarians, and Ca V 2A and Ca V 2B in platyhelminthes [2,4,36].…”

Section: Phylogenetic Analyses Suggest Deep Conservation Of Mint Inte...supporting

confidence: 90%

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Mint/X11 PDZ domains from non-bilaterian animals recognize and bind Ca_V2 calcium channel C-terminiin vitro.

Harracksingh,

Singh,

Mayorova

et al. 2024

Preprint

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PDZ domain mediated interactions with voltage-gated calcium (CaV) channel C-termini play important roles in localizing and compartmentalizing membrane Ca2+signaling. The first such interaction discovered was between the neuronal multi-domain protein Mint-1, and the presynaptc calcium channel CaV2.2 in mammals. Although the physiological significance of this interaction is unclear, its occurrence in vertebrates and bilaterian invertebrates suggests important and conserved functions. In this study, we explore the evolutionary origins of Mint and its interaction with CaV2 channels. Phylogenetic and structuralin silicoanalyses revealed that Mint is an animal-specific gene, like CaV2 channels, which bears a highly divergent N-terminus but strongly conserved C-terminus comprised of a phosphotyrosine binding domain, two tandem PDZ domains (PDZ-1 and PDZ-2), and a C-terminal auto-inhibitory element that binds and inhibits PDZ-1. Also deeply conserved are other Mint interacting proteins, namely amyloid precursor and related proteins, presenilins, neurexin, as well as CASK and Veli which form a tripartite complex with Mint in bilaterians. Through yeast 2-hybrid and bacterial 2-hybrid experiments, we show that Mint and CaV2 channels from cnidarians and placozoans interactin vitro, andin situhybridization revealed co-expression of corresponding transcripts in dissociated neurons from the cnidarianNematostella vectensis. Unexpectedly, the Mint orthologue from the ctenophoreHormiphora californiensiswas able to strongly bind the divergent C-terminal ligands of cnidarian and placozoan CaV2 channels, despite neither the ctenophore Mint, nor the placozoan and cnidarian orthologues, binding the ctenophore CaV2 channel C-terminus. Altogether, our analyses provide a model for the emergence of this interaction in early animals first via adoption of a PDZ ligand by CaV2 channels, followed by sequence changes in the ligand that caused a modality switch for binding to Mint.

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Section: Resultssupporting

confidence: 90%

Section: Phylogenetic Analyses Suggest Deep Conservation Of Mint Inte...supporting

confidence: 90%

Mint/X11 PDZ domains from non-bilaterian animals recognize and bind Ca_V2 calcium channel C-terminiin vitro.

Harracksingh,

Singh,

Mayorova

et al. 2024

Preprint

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“…Ca V channels have been phylogenetically classified into three families: Ca V 1, Ca V 2 and Ca V 3 7,8 . Based on their active voltage, Ca V channels also are categorized into two families: high‐voltage‐activated (HVA) Ca V channels including Ca V 1 and Ca V 2, and low‐voltage‐activated (LVA) Ca V channels including Ca V 3 7 . Toxins targeting Ca V channels are usually described with the Greek letter ω in their name 9 .…”

Section: Introductionmentioning

confidence: 99%

“…7,8 Based on their active voltage, Ca V channels also are categorized into two families: high-voltage-activated (HVA) Ca V channels including Ca V 1 and Ca V 2, and low-voltage-activated (LVA) Ca V channels including Ca V 3. 7 Toxins targeting Ca V channels are usually described with the Greek letter ω in their name. 9 The ω-agatoxins from the American funnel web spider Agelenopsis aperta are among the best-studied spider neurotoxins and have diverse specificity against various subtypes of Ca V channels.…”

Section: Introductionmentioning

confidence: 99%

“…Among these ion channels, voltage‐gated calcium (Ca V ) channels play a fundamental role in neuronal, muscular and cardiac functions. Ca V channels have been phylogenetically classified into three families: Ca V 1, Ca V 2 and Ca V 3 7,8 . Based on their active voltage, Ca V channels also are categorized into two families: high‐voltage‐activated (HVA) Ca V channels including Ca V 1 and Ca V 2, and low‐voltage‐activated (LVA) Ca V channels including Ca V 3 7 .…”

Section: Introductionmentioning

confidence: 99%

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Insecticidal toxicity of ω‐Atypitoxin‐Cs1a and its inhibitory effects on insect voltage‐gated calcium channels

Yan

Han

et al. 2023

Pest Management Science

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BACKGROUNDExcessive use of chemical insecticides raises concerns about insecticide resistance, urging the development of novel insecticides. Peptide neurotoxins from spider venom are an incredibly rich source of ion channel modulators with potent insecticidal activity. A neurotoxin U1‐Atypitoxin‐Cs1a from the spider Calommata signata was annotated previously. It was of interest to investigate its insecticidal activity and potential molecular targets.RESULTSCs1a was heterologously expressed, purified and pharmacologically characterized here. The recombinant neurotoxin inhibited high‐voltage‐activated calcium channel currents with an median inhibitory concentration (IC50) value of 0.182 ± 0.026 μm on cockroach DUM neurons and thus was designated as ω‐Atypitoxin‐Cs1a. The recombinant Cs1a was toxic to three insect pests of agricultural importance, Nilaparvata lugens, Spodoptera frugiperda and Plutella xylostella with median lethal concentration (LD50) values of 0.121, 0.172 and 0.356 nmol g−1, respectively, at 24 h postinjection. Cs1a was equivalently toxic to both insecticide‐susceptible and ‐resistant insects. Cs1a exhibited low toxicity to Danio rerio with an LD50 of 2.316 nmol g−1.CONCLUSIONOur results suggest that ω‐Atypitoxin‐Cs1a is a potent CaV channel inhibitor and an attractive candidate reagent for pest control and resistance management. © 2023 Society of Chemical Industry.

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Mint/X11 PDZ domains from non-bilaterian animals recognize and bind CaV2 calcium channel C-termini in vitro

Harracksingh,

Singh,

Mayorova

et al. 2024

Sci Rep

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PDZ domain mediated interactions with voltage-gated calcium (CaV) channel C-termini play important roles in localizing membrane Ca2+ signaling. The first such interaction was described between the scaffolding protein Mint-1 and CaV2.2 in mammals. In this study, we show through various in silico analyses that Mint is an animal-specific gene with a highly divergent N-terminus but a strongly conserved C-terminus comprised of a phosphotyrosine binding domain, two tandem PDZ domains (PDZ-1 and PDZ-2), and a C-terminal auto-inhibitory element that binds and inhibits PDZ-1. In addition to CaV2 chanels, most genes that interact with Mint are also deeply conserved including amyloid precursor proteins, presenilins, neurexin, and CASK and Veli which form a tripartite complex with Mint in bilaterians. Through yeast and bacterial 2-hybrid experiments, we show that Mint and CaV2 channels from cnidarians and placozoans interact in vitro, and in situ hybridization revealed co-expression in dissociated neurons from the cnidarian Nematostella vectensis. Unexpectedly, the Mint orthologue from the ctenophore Hormiphora californiensis strongly bound the divergent C-terminal ligands of cnidarian and placozoan CaV2 channels, despite neither the ctenophore Mint, nor the placozoan and cnidarian orthologues, binding the ctenophore CaV2 channel C-terminus. Altogether, our analyses suggest that the capacity of Mint to bind CaV2 channels predates bilaterian animals, and that evolutionary changes in CaV2 channel C-terminal sequences resulted in altered binding modalities with Mint.

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Voltage-Gated Calcium Channels in Invertebrates

Cited by 5 publications

References 311 publications

Mint/X11 PDZ domains from non-bilaterian animals recognize and bind Ca_V2 calcium channel C-terminiin vitro.

Mint/X11 PDZ domains from non-bilaterian animals recognize and bind Ca_V2 calcium channel C-terminiin vitro.

Insecticidal toxicity of ω‐Atypitoxin‐Cs1a and its inhibitory effects on insect voltage‐gated calcium channels

Mint/X11 PDZ domains from non-bilaterian animals recognize and bind CaV2 calcium channel C-termini in vitro

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Voltage-Gated Calcium Channels in Invertebrates

Cited by 5 publications

References 311 publications

Mint/X11 PDZ domains from non-bilaterian animals recognize and bind CaV2 calcium channel C-terminiin vitro.

Mint/X11 PDZ domains from non-bilaterian animals recognize and bind CaV2 calcium channel C-terminiin vitro.

Insecticidal toxicity of ω‐Atypitoxin‐Cs1a and its inhibitory effects on insect voltage‐gated calcium channels

Mint/X11 PDZ domains from non-bilaterian animals recognize and bind CaV2 calcium channel C-termini in vitro

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Product

Resources

About

Mint/X11 PDZ domains from non-bilaterian animals recognize and bind Ca_V2 calcium channel C-terminiin vitro.

Mint/X11 PDZ domains from non-bilaterian animals recognize and bind Ca_V2 calcium channel C-terminiin vitro.