Evolutionary insights into T-type Ca2+ channel structure, function, and ion selectivity from the <i>Trichoplax adhaerens</i> homologue

Smith, Carolyn L.; Abdallah, Salsabil; Wong, YW; Le, Phuong; Harracksingh, Alicia N.; Artinian, Liana; Tamvacakis, Arianna N; Rehder, Vincent; Reese, Thomas S.; Senatore, Adriano

doi:10.1085/jgp.201611683

Cited by 36 publications

(57 citation statements)

References 113 publications

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“…Trichoplax also retains both homologues, but our mRNA expression and localization studies of RIMs and Ca V s point to low level expression (Figures 1 and S1), making it difficult to interpret their cell-type expression profiles and possible roles. We note that in ongoing studies being carried out in our lab, all three Trichoplax Ca V channels express in vitro to conduct voltage-sensitive Ca 2+ that resemble those of Ca V 1-Ca V 3 homologues from other animals ((Smith, et al 2017); unpublished data). However, the role of Ca V channels and transient membrane Ca 2+ signaling in Trichoplax biology is unknown.…”

Section: Discussionmentioning

confidence: 83%

“…The apparent absence of synapses in Trichoplax is not reflected by its expressed gene set, which in addition to RIM includes homologues for key active zone proteins such as SNARE and associated proteins, and scaffolding proteins that interact with Ca V 2 calcium channels at nerve terminals such as Mint, CASK, Liprin-α, ELKS and RIM-BP (Figure 1A and B). Trichoplax is also the most early-diverging animal with homologues for all three metazoan Ca V channel types: Ca V 1, Ca V 2 and Ca V 3 (Senatore, et al 2012; Moran and Zakon 2014; Senatore, et al 2016; Smith, et al 2017).…”

Section: Resultsmentioning

confidence: 99%

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Early metazoan origin and multiple losses of a novel clade of RIM pre-synaptic calcium channel scaffolding protein homologues

Piekut

Wong

Walker

et al. 2020

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The precise localization of Ca V 2 voltage-gated calcium channels at the synapse active zone requires various interacting proteins, of which, Rab3 interacting molecule or RIM is particularly important. In vertebrates, RIM has been shown to interact with Ca V 2 channels in vitro via a PDZ domain that binds to the extreme C-termini of the channels at acidic ligand motifs of D/E-D/E/H-WC-COOH . Here, we describe a previously undescribed clade of RIM proteins bearing homologous domain architectures as known RIM homologues, but some notable differences including key amino acids associated with PDZ domain ligand specificity. This novel RIM emerged near the stem lineage of metazoans and underwent extensive losses, but is retained in select animals including the early-diverging placozoan Trichoplax adhaerens, and molluscs. RNA expression and localization studies in Trichoplax and the mollusc snail Lymnaea stagnalis indicate differential regional/tissue type expression, but overlapping expression in single isolated neurons from Lymnaea. Ctenophores, the most early-diverging animals with synapses, are unique among animals with nervous systems in that they lack the canonical RIM, bearing only the newly identified homologue.Through phylogenetic analysis, we find that Ca V 2 channel D/E-D/E/H-WC-COOH like PDZ ligand motifs were present the common ancestor of cnidarians and bilaterians. We also delineate some deeply conserved C-terminal structures that distinguish Ca V 1 from Ca V 2 channels, and Ca V 1/Ca V 2 from Ca V 3 channels.Average counts of fluorescent granules within regions of the animal characterized by distinct celltype content (i.e. the edge, fiber cell zone and lipophil cell zone (Mayorova, et al. 2019)), revealed that II-RIM is more abundantly expressed than I-RIM overall and in each region ( Figure 1F; p-values for Tukey's tests after one-way ANOVAs: edge <0.05; fiber zone <0.0005; lipophil zone <0.00005; sum of regions <0.00005; ANOVA for separate regions: df = 5, F = 17.1, p = 2.1E-15; ANOVA for regions combined: df = 1, F = 24.5, p = 2.1E-6). Notably, these patterns are consistent with mRNA expression levels measured as average transcripts per million (TPM) in the transcriptome data, where II-RIM is more abundantly expressed than I-RIM at the whole animal level ( Figure 1B). Also consistent were the average TPM values and counted granules for in situ hybridization of the three Trichoplax Ca V channels (Ca V 1-Ca V 3), where TPM and granule counts for Ca V 1 were significantly higher compared to Ca V 2 and Ca V 3 within edge and lipophil zones and all three regions combined (i.e. compare Figure 1B and F) (p-values for Tukey's tests after one-way ANOVAs of granule counts: Ca V 1 vs. Ca V 2 edge <0.00005; Ca V 1 vs.Ca V 2 lipophil zone <0.00005; Ca V 1 vs. Ca V 2 total <0.00005; Ca V 1 vs. Ca V 3 edge <0.00005; Ca V 1 vs.Ca V 3 lipophil zone <0.00005; Ca V 1 vs. Ca V 3 total <0.00005; ANOVA for separate regions: df = 8, F = 86.8, p = 0; ANOVA for regions combined: df = 2, F = 159.0, p = 0;). Indeed, in spite of...

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Section: Discussionmentioning

confidence: 83%

Section: Resultsmentioning

confidence: 99%

Early metazoan origin and multiple losses of a novel clade of RIM pre-synaptic calcium channel scaffolding protein homologues

Piekut

Wong

Walker

et al. 2020

Preprint

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“…Clearly, functional studies of distinct cell types, coupled with electrophysiology and/or optical recording, are a necessary next step in understanding the roles of electrical and calcium signaling in and play a major role in regulating cellular excitability. We found that despite its significant divergence at the amino acid sequence level, the Trichoplax Ca v 3 channel conducts low-voltage activated Ca 2+ currents with hallmark features for this channel type that are required for regulating excitability [108]. By extension, it is plausible that other and perhaps numerous Trichoplax ion channels share core functional attributes with their counterparts from other animals, which could be co-expressed in varying functional assemblages as occurs in neurons to produce alternate modalities of cellular excitation.…”

Section: Discussionmentioning

confidence: 92%

Transcriptome profiling of Trichoplax adhaerens highlights its digestive epithelium and a rich set of genes for fast electrogenic and slow neuromodulatory cellular signaling

Wong

Elkhatib

et al. 2019

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Background Trichoplax adhaerens is a fascinating early-diverging animal that lacks a nervous system and synapses, and yet is capable of directed motile feeding behavior culminating in the external digestion of microorganisms by secreted hydrolytic enzymes. The mechanisms by which Trichoplax cells communicate with each other to coordinate their activity and behavior is unclear, though recent studies have suggested that secreted regulatory peptides might be involved.Results Here, we generated a high quality mRNA transcriptome of Trichoplax adhaerens , and predicted secreted proteins to identify gene homologues for digestion, development, immunity, cell adhesion, and peptide signaling. Detailed annotation of the expressed Trichoplax gene set also identified a nearly complete set of electrogenic genes involved in fast neural signalling, plus a set of 665 G-protein coupled receptors that in the nervous system integrate with fast signalling machinery to modulate cellular excitability. Furthermore, Trichoplax expresses an array of genes involved in intracellular signaling, including the key effector enzymes protein kinases A and C that functionally link fast and slow cellular signaling. Also identified were nearly complete sets of pre- and post-synaptic scaffolding genes, most encoding appropriate protein domain architectures. Notably, the Trichoplax proteome was found to bear slightly reduced counts of synaptic protein interaction domains such as PDZ, SH3 and C2 compared to other animals, but abundance of these domains did not appear to predict the presence of synapses in early-diverging groups.Conclusions Despite its apparent cellular and morphological simplicity, Trichoplax expresses a rich set of genes involved in complex animal traits. The transcriptome presented here adds a valuable additional resource for molecular studies on Trichoplax genes, exemplified by our ability to clone cDNAs for nine full-length acid sensing ion channel proteins with almost perfect matches with their corresponding transcriptome sequences.

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“…In Hydrozoan cnidarians, the nervous system is thought to be derived from I-cells that orginate in the endomesoderm (gastroderm) during embryonic development [89][90][91], although sensory cells can emerge from I-cell free animals [92,93]. In the absence of a true nervous (or musculature) system, neuropeptide and calcium signaling play a role in complex behaviors of these animals [94,95]. Our findings, although suggestive, require greater analysis and further study to truly understand how these and other developmental genes shape the body of Trichoplax.…”

Section: Discussionmentioning

confidence: 99%

The radial expression of dorsal-ventral patterning genes in placozoans,Trichoplax adhaerens,argues for an oral-aboral axis

Bobkov

Ryan

et al. 2018

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The placozoans are a morphologically simplistic group of marine animals found globally in tropical and subtropical environments. They consist of a single named species, Trichoplax adhaerens and have roughly six morphologically distinct cell types. With a sequenced genome, a limited number of cell-types and a simple flattened morphology, Trichoplax is an ideal model organism to understand cellular dynamics and tissue patterning in the first animals. Using new approaches for identification of gene expression patterns this research looks at the relationship of Chordin/TgfB signaling and the axial patterning system of Placozoa. Our results suggest that placozoans have an oral-aboral axis similar to cnidarians and that the parahoxozoan ancestor (common ancestor of Placozoa and Cnidaria) was likely radially symmetric.

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Evolutionary insights into T-type Ca2+ channel structure, function, and ion selectivity from the Trichoplax adhaerens homologue

Cited by 36 publications

References 113 publications

Early metazoan origin and multiple losses of a novel clade of RIM pre-synaptic calcium channel scaffolding protein homologues

Early metazoan origin and multiple losses of a novel clade of RIM pre-synaptic calcium channel scaffolding protein homologues

Transcriptome profiling of Trichoplax adhaerens highlights its digestive epithelium and a rich set of genes for fast electrogenic and slow neuromodulatory cellular signaling

The radial expression of dorsal-ventral patterning genes in placozoans,Trichoplax adhaerens,argues for an oral-aboral axis

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