{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlthough the inquiry requested a summary of SNORD26 function, none of the provided abstracts report any role for SNORD26. Instead, they collectively focus on the Ca(v)β3 subunit of voltage‐gated calcium channels and its pleiotropic modulatory functions in diverse cell types. For example, in pancreatic β‐cells, deletion of Ca(v)β3 enhances glucose‐induced cytoplasmic Ca²⁺ oscillations, which correlates with increased insulin secretion and improved glucose homeostasis (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "]).\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the nervous and immune systems Ca(v)β3 is shown to be pivotal. In hippocampal neurons, Ca(v)β3 negatively regulates NMDA receptor activity and thereby influences synaptic plasticity and cognitive behaviors (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "]). Moreover, in naive CD8⁺ T lymphocytes, loss of Ca(v)β3 leads to destabilization of channel complexes, causing reduced global Ca²⁺ entry and compromising cell survival (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "]).\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPeripheral roles of Ca(v)β3 have also been elucidated. In the olfactory receptor neurons of the nasal epithelium, β3 deficiency results in heightened neuronal responses to odorants (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "]). In smooth muscle cells, studies indicate that while the overall L-type Ca²⁺ current properties remain largely intact, Ca(v)β3 subtly shifts voltage activation, and its absence alters stimulated renal Ca²⁺ transport (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "]). In adrenal chromaffin cells, β3 deletion decreases L- and N-type currents yet paradoxically facilitates catecholamine release via enhanced inositol 1,4,5-trisphosphate production (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "]).\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional studies reveal that Ca(v)β3 contributes to specialized cellular functions. In the cochlea, loss of β3 in outer hair cells alters current amplitudes and kinetics, affecting auditory signal transduction (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "]). In activated dendritic cells, such as Langerhans cell–like populations, upregulation of Ca(v)β3 is associated with maturation responses (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "]). Moreover, enhanced Ca(v)β3 activity appears to influence fibroblast migration and may play a part in modulating endothelial Ca²⁺ signaling that is vital for blood–brain barrier integrity (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "]).\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDevelopmental and tissue-specific investigations further underscore the nuanced contribution of Ca(v)β3. In cardiac tissue, for instance, altering the stoichiometry between the α₁ and β subunits compromises Ca²⁺ channel trafficking and myocyte contractility (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "]). In the brain, spatiotemporal expression analyses indicate that Ca(v)β3, along with other β isoforms, supports the maturation of synaptic connections in the hippocampus and cerebellum (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "]). Finally, in the placenta Ca(v)β3 is upregulated in hyperplastic conditions, although its deletion yields only subtle architectural changes, suggesting redundancy with other regulatory mechanisms (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "]).\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these studies emphasize that while SNORD26 is not implicated in the reported findings, the Ca(v)β3 subunit plays a critical role in fine-tuning calcium channel function. Its regulatory impact spans the modulation of Ca²⁺ oscillations, receptor-operated Ca²⁺ entry, and downstream signaling in endocrine, neural, immune, and peripheral tissues, thereby influencing processes from insulin secretion and synaptic plasticity to catecholamine release and vascular regulation.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Per-Olof Berggren, Shao-Nian Yang, Manabu Murakami, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Removal of Ca2+ channel beta3 subunit enhances Ca2+ oscillation frequency and insulin exocytosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2004.09.033"}], "href": "https://doi.org/10.1016/j.cell.2004.09.033"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15479643"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15479643"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Daejong Jeon, Inseon Song, William Guido, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ablation of Ca2+ channel beta3 subunit leads to enhanced N-methyl-D-aspartate receptor-dependent long term potentiation and improved long term memory."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M800816200"}], "href": "https://doi.org/10.1074/jbc.M800816200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18339621"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18339621"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Manabu Murakami, Takayoshi Ohba, Feng Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Modified sympathetic nerve system activity with overexpression of the voltage-dependent calcium channel beta3 subunit."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M802319200"}], "href": "https://doi.org/10.1074/jbc.M802319200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18628210"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18628210"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Mithilesh K Jha, Abdallah Badou, Marcel Meissner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Defective survival of naive CD8+ T lymphocytes in the absence of the beta3 regulatory subunit of voltage-gated calcium channels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni.1793"}], "href": "https://doi.org/10.1038/ni.1793"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19838200"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19838200"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Takeshi Shiraiwa, Makoto Kashiwayanagi, Toshihiko Iijima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of the calcium channel beta3 subunit in olfactory signal transduction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2007.02.063"}], "href": "https://doi.org/10.1016/j.bbrc.2007.02.063"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17335778"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17335778"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Brigitte Held, Volodymyr Tsvilovskyy, Marcel Meissner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ca2+ channel currents and contraction in CaVbeta3-deficient ileum smooth muscle from mouse."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Calcium (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ceca.2007.04.013"}], "href": "https://doi.org/10.1016/j.ceca.2007.04.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17580090"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17580090"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "José F Bernardo, Clara E Magyar, W Bruce Sneddon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impaired renal calcium absorption in mice lacking calcium channel beta 3 subunits."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Can J Physiol Pharmacol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1139/y09-035"}], "href": "https://doi.org/10.1139/y09-035"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19767875"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19767875"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Toshio Ohta, Takayoshi Ohba, Takashi Suzuki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Decreased calcium channel currents and facilitated epinephrine release in the Ca2+ channel beta3 subunit-null mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2010.01.036"}], "href": "https://doi.org/10.1016/j.bbrc.2010.01.036"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20144588"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20144588"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Stephanie Kuhn, Martina Knirsch, Lukas Rüttiger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ba2+ currents in inner and outer hair cells of mice lacking the voltage-dependent Ca2+ channel subunits beta3 or beta4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Channels (Austin) (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/chan.3.5.9774"}], "href": "https://doi.org/10.4161/chan.3.5.9774"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19755851"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19755851"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Matthias Bros, Nadine Dexheimer, Ralf Ross, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential gene expression analysis identifies murine Cacnb3 as strongly upregulated in distinct dendritic cell populations upon stimulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2010.10.013"}], "href": "https://doi.org/10.1016/j.gene.2010.10.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21040760"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21040760"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Anouar Belkacemi, Xin Hui, Barbara Wardas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IP"}, {"type": "a", "children": [{"type": "t", "text": "sub"}], "href": "sub"}, {"type": "t", "text": "3"}, {"type": "a", "children": [{"type": "t", "text": "/sub"}], "href": "/sub"}, {"type": "t", "text": " Receptor-Dependent Cytoplasmic Ca"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "2+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " Signals Are Tightly Controlled by Cavβ3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2018.01.010"}], "href": "https://doi.org/10.1016/j.celrep.2018.01.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29386119"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29386119"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Damian Martus, Sarah K Williams, Kira Pichi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cavβ3 Contributes to the Maintenance of the Blood-Brain Barrier and Alleviates Symptoms of Experimental Autoimmune Encephalomyelitis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/ATVBAHA.124.321141"}], "href": "https://doi.org/10.1161/ATVBAHA.124.321141"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38957986"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38957986"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Vladimir Serikov, Ilona Bodi, Sheryl E Koch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mice with cardiac-specific sequestration of the beta-subunit of the L-type calcium channel."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/S0006-291X(02)00396-0"}], "href": "https://doi.org/10.1016/S0006-291X(02"}, {"type": "t", "text": "00396-0) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12054671"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12054671"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Clotilde Ferrándiz-Huertas, Mercedes Gil-Mínguez, Rafael Luján "}, {"type": "b", "children": [{"type": "t", "text": "Regional expression and subcellular localization of the voltage-gated calcium channel β subunits in the developing mouse brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurochem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1471-4159.2012.07853.x"}], "href": "https://doi.org/10.1111/j.1471-4159.2012.07853.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22737983"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22737983"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "U Singh, T Sun, C Looman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and function of the gene encoding the voltage-dependent calcium channel beta3-subunit in the mouse placenta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Placenta (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.placenta.2006.05.007"}], "href": "https://doi.org/10.1016/j.placenta.2006.05.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16822546"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16822546"}]}]}]}