{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Harracksingh AN"],"funding":["NIH Grant","Ontario Graduate Scholarship","Ontario Early Researcher Award","NSERC Discovery Accelerator Supplement","NSERC Discovery","Canadian Foundation for Innovation Grant","NSERC Canadian Graduate Scholarship","NIGMS NIH HHS"],"pagination":["21615"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11405698"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(1)"],"pubmed_abstract":["PDZ domain mediated interactions with voltage-gated calcium (Ca<sub>V</sub>) channel C-termini play important roles in localizing membrane Ca<sup>2+</sup> signaling. The first such interaction was described between the scaffolding protein Mint-1 and Ca<sub>V</sub>2.2 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 Ca<sub>V</sub>2 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 Ca<sub>V</sub>2 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 Ca<sub>V</sub>2 channels, despite neither the ctenophore Mint, nor the placozoan and cnidarian orthologues, binding the ctenophore Ca<sub>V</sub>2 channel C-terminus. Altogether, our analyses suggest that the capacity of Mint to bind Ca<sub>V</sub>2 channels predates bilaterian animals, and that evolutionary changes in Ca<sub>V</sub>2 channel C-terminal sequences resulted in altered binding modalities with Mint."],"journal":["Scientific reports"],"pubmed_title":["Mint/X11 PDZ domains from non-bilaterian animals recognize and bind Ca<sub>V</sub>2 calcium channel C-termini in vitro."],"pmcid":["PMC11405698"],"funding_grant_id":["R01 GM133936","RGPIN-2021-03557","R01GM133936","RGPAS-2021-00002","RGPIN-2023-05615","40684","35297","ER17-13-247"],"pubmed_authors":["Islam IM","Senatore A","Harracksingh AN","Erclik T","Singh A","Mayorova TD","Bejoy B","Elkhatib W","McEdwards G","Currie MA","Hornbeck J","Gauberg J","Taha A","Noyes M"],"additional_accession":[]},"is_claimable":false,"name":"Mint/X11 PDZ domains from non-bilaterian animals recognize and bind Ca<sub>V</sub>2 calcium channel C-termini in vitro.","description":"PDZ domain mediated interactions with voltage-gated calcium (Ca<sub>V</sub>) channel C-termini play important roles in localizing membrane Ca<sup>2+</sup> signaling. The first such interaction was described between the scaffolding protein Mint-1 and Ca<sub>V</sub>2.2 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 Ca<sub>V</sub>2 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 Ca<sub>V</sub>2 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 Ca<sub>V</sub>2 channels, despite neither the ctenophore Mint, nor the placozoan and cnidarian orthologues, binding the ctenophore Ca<sub>V</sub>2 channel C-terminus. Altogether, our analyses suggest that the capacity of Mint to bind Ca<sub>V</sub>2 channels predates bilaterian animals, and that evolutionary changes in Ca<sub>V</sub>2 channel C-terminal sequences resulted in altered binding modalities with Mint.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Sep","modification":"2026-06-02T06:31:02.707Z","creation":"2025-04-06T16:09:53.924Z"},"accession":"S-EPMC11405698","cross_references":{"pubmed":["39284887"],"doi":["10.1038/s41598-024-70652-8"]}}