Ctenophores and parahoxozoans independently evolved complex and functionally diverse sets of voltage-gated K+channels DOI Open Access
Benjamin T. Simonson, Zhaoyang Jiang, Joseph F. Ryan

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 11, 2024

Abstract The ctenophore species Mnemiopsis leidyi is known to have a large set of voltage-gated K + channels, but little about the functional diversity these channels or evolutionary history this gene family in other species. Here, we searched genomes two additional species, Beroe ovata and Hormiphora californensis , for functionally expressed subset M. channels. We found that last common ancestor three disparate lineages probably had at least 33 Two genes belong EAG family, remaining 31 Shaker form single clade within animal/choanoflagellate phylogeny. additionally evidence 10 transcriptome early branching lineage Euplokamis dunlapae suggesting diversification was already underway evolution. 16 Shakers they encode diverse array conductances with orthologs many classic subtypes cnidarians bilaterians. Ctenophores therefore appear independently evolved much channel shared between

Language: Английский

Ctenophores and parahoxozoans independently evolved functionally diverse voltage-gated K+ channels DOI
Benjamin T. Simonson,

Zhaoyang Jiang,

Joseph F. Ryan

et al.

The Journal of General Physiology, Journal Year: 2025, Volume and Issue: 157(3)

Published: Feb. 27, 2025

The ctenophore species Mnemiopsis leidyi is known to have a large set of voltage-gated K+ channels, but little about the functional diversity these channels or their evolutionary history in other species. Here, we searched genomes two additional species, Beroe ovata and Hormiphora californensis, for functionally expressed subset M. channels. We found that last common ancestor three disparate lineages probably had at least 33 Two genes belong EAG family, remaining 31 Shaker family form single clade within animal/choanoflagellate phylogeny. additionally evidence 10 transcriptome early branching lineage Euplokamis dunlapae, suggesting diversification was already underway evolution. 16 Shakers they encode diverse array conductances with orthologs many classic subtypes cnidarians bilaterians. Analysis data show are wide variety cell types, including neurons, muscle, comb cells, colloblasts. Ctenophores therefore appear independently evolved much channel shared between

Language: Английский

Citations

2
A broad survey of choanoflagellates revises the evolutionary history of the Shaker family of voltage-gated K + channels in animals DOI Creative Commons
Timothy Jegla, Benjamin T. Simonson, J. David Spafford

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(30)

Published: July 17, 2024

The Shaker family of voltage-gated K

Language: Английский

Citations

5
Functional analysis of ctenophore Shaker K+ channels: N-type inactivation in the animal roots DOI
Benjamin T. Simonson,

Max Jegla,

Joseph F. Ryan

et al.

Biophysical Journal, Journal Year: 2024, Volume and Issue: 123(14), P. 2038 - 2049

Published: Jan. 30, 2024

Language: Английский

Citations

4
Identification and classification of ion-channels across the tree of life: Insights into understudied CALHM channels DOI Open Access
Rahil Taujale, Sung Jin Park, Nathan Gravel

et al.

Published: May 9, 2025

Abstract The ion channel (IC) genes encoded in the human genome play fundamental roles cellular functions and disease are one of largest classes druggable proteins. However, limited knowledge diverse molecular carried out by ICs presents a major bottleneck developing selective chemical probes for modulating their states. wealth sequence data available on from organisms provides valuable source untapped information illuminating unique modes regulation functional specialization. extensive diversification IC sequences lack unified resource present challenge effectively using existing research. Here, we perform integrative mining sequence, structure, 419 across disparate sources, including literature leveraging advances large language models to annotate curate full complement “channelome”. We employ well-established orthology inference approach identify extend orthologs above 48,000. show that depth conservation taxonomic representation can further be translated similarities clustering them into functionally relevant groups, which used downstream prediction understudied members. demonstrate this delineating co-conserved patterns characteristic family Calcium Homeostasis Modulator (CALHM) ICs. Through mutational analysis residues altered diseases electrophysiological studies, evolutionary-constrained significantly alter gating functions. Thus, providing new tools resources performing comparative analyses ICs, study addresses needs community groundwork accelerating characterization dark channels therapeutic intervention.

Language: Английский

Citations

0
Identification and classification of ion-channels across the tree of life: Insights into understudied CALHM channels DOI Open Access
Rahil Taujale, Sung Jin Park, Nathan Gravel

et al.

Published: May 9, 2025

Abstract The ion channel (IC) genes encoded in the human genome play fundamental roles cellular functions and disease are one of largest classes druggable proteins. However, limited knowledge diverse molecular carried out by ICs presents a major bottleneck developing selective chemical probes for modulating their states. wealth sequence data available on from organisms provides valuable source untapped information illuminating unique modes regulation functional specialization. extensive diversification IC sequences lack unified resource present challenge effectively using existing research. Here, we perform integrative mining sequence, structure, 419 across disparate sources, including literature leveraging advances large language models to annotate curate full complement “channelome”. We employ well-established orthology inference approach identify extend orthologs above 48,000. show that depth conservation taxonomic representation can further be translated similarities clustering them into functionally relevant groups, which used downstream prediction understudied members. demonstrate this delineating co-conserved patterns characteristic family Calcium Homeostasis Modulator (CALHM) ICs. Through mutational analysis residues altered diseases electrophysiological studies, evolutionary-constrained significantly alter gating functions. Thus, providing new tools resources performing comparative analyses ICs, study addresses needs community groundwork accelerating characterization dark channels therapeutic intervention.

Language: Английский

Citations

0
Molecular Insights into the Low Complexity Secreted Venom of Calliactis polypus DOI Creative Commons
Hayden L. Smith, Daniel Broszczak, Scott E. Bryan

et al.

Genome Biology and Evolution, Journal Year: 2024, Volume and Issue: 16(8)

Published: July 17, 2024

Abstract Sea anemones are venomous animals that rely on their venom for prey capture, defense against predators, and intraspecific competition. Currently, comprehensive molecular evolutionary analyses of the toxin repertoire sea limited by a lack proteomic data most species. In this study, proteo-transcriptomic analysis was used to expand our knowledge proteinaceous components anemone determining secreted proteome Calliactis polypus. Electromechanical stimulation obtain C. We identified low complexity dominated toxins with similarity known neurotoxins, as well six novel candidates. The putative candidates were found be taxonomically restricted species from superfamily Metridioidea. Furthermore, polypus had only three in common acontia same little closely related Overall, demonstrates regionalized lineage-specific variability abundance is among Moreover, supports idea peptide neurotoxins make up dominant arsenal anemones.

Language: Английский

Citations

2
Elucidation of Medusozoan (Jellyfish) Venom Constituent Activities Using Constellation Pharmacology DOI Creative Commons
Angel A. Yanagihara, Matías L. Giglio,

Kikiana Hurwitz

et al.

Toxins, Journal Year: 2024, Volume and Issue: 16(10), P. 447 - 447

Published: Oct. 17, 2024

Within the phylum Cnidaria, sea anemones (class Anthozoa) express a rich diversity of ion-channel peptide modulators with biomedical applications, but corollary discoveries from jellyfish (subphylum Medusozoa) are lacking. To bridge this gap, bioactivities previously unexplored proteinaceous and small molecular weight (~15 kDa to 5 kDa) venom components were assessed in mouse dorsal root ganglia (DRG) high-content calcium-imaging assay, known as constellation pharmacology. While addition crude led nonspecific cell death Fura-2 signal leakage due pore-forming activity, purified fractions demonstrated three main, concentration-dependent reversible effects on defined heterogeneous types found primary cultures DRG. These phenotypic responses herein referred phenotype A, B C: excitatory amplification (A) or inhibition (B) KCl-induced calcium signals, test compound-induced disturbances baseline levels (C). Most notably, certain

Language: Английский

Citations

1
Decoding the Functional Interactome of Non-Model Organisms with PHILHARMONIC DOI Creative Commons
Samuel Sledzieski,

C Versavel,

Rohit Singh

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 29, 2024

Protein-protein interaction (PPI) networks are a fundamental resource for modeling cellular and molecular function, large sophisticated toolbox has been developed to leverage their structure topological organization predict the functional roles of under-studied genes, proteins, pathways. However, overwhelming majority experimentally-determined interactions from which such constructed come small number well-studied model organisms. Indeed, most species lack even single in these databases, much less network enable analysis methods computational PPI prediction too noisy apply directly. We introduce PHILHARMONIC, novel approach that couples deep learning

Language: Английский

Citations

0
Ctenophores and parahoxozoans independently evolved complex and functionally diverse sets of voltage-gated K+channels DOI Open Access
Benjamin T. Simonson, Zhaoyang Jiang, Joseph F. Ryan

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 11, 2024

Abstract The ctenophore species Mnemiopsis leidyi is known to have a large set of voltage-gated K + channels, but little about the functional diversity these channels or evolutionary history this gene family in other species. Here, we searched genomes two additional species, Beroe ovata and Hormiphora californensis , for functionally expressed subset M. channels. We found that last common ancestor three disparate lineages probably had at least 33 Two genes belong EAG family, remaining 31 Shaker form single clade within animal/choanoflagellate phylogeny. additionally evidence 10 transcriptome early branching lineage Euplokamis dunlapae suggesting diversification was already underway evolution. 16 Shakers they encode diverse array conductances with orthologs many classic subtypes cnidarians bilaterians. Ctenophores therefore appear independently evolved much channel shared between

Language: Английский

Citations

0