{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlthough none of the provided abstracts actually mention SORCS3‑AS1, they instead detail the multifaceted functions of the γ‑subunit of Na,K‑ATPase encoded by FXYD2. In renal tissue, FXYD2 plays a key regulatory and structural role: its expression and splice‐variant usage modulate the enzyme’s affinity for Na⁺ and contribute to the thermal stability of Na,K‑ATPase under both basal and hypertonic conditions. Loss of FXYD2 alters ion transport kinetics and impairs cellular adaptation to osmotic stress, underscoring its importance in maintaining ion balance and cell survival in the kidney."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the neural context, FXYD2 contributes to the modulation of neuronal excitability and pain processing. In nociceptive sensory neurons, FXYD2 interacts with the Na,K‑ATPase to depress its activity, leading to membrane depolarization and the facilitation of pain signals during inflammatory conditions. Moreover, in dorsal root ganglion neurons, FXYD2 is specifically expressed in mechanoceptive and non‐peptidergic nociceptors where its transcription is controlled by key developmental and injury‐responsive signaling pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, FXYD2 impacts metabolic and inflammatory processes beyond its canonical role in ion transport. In pancreatic beta cells, absence of FXYD2 leads to enhanced Akt signaling, promoting beta cell proliferation and hyperinsulinemia, thereby improving glucose tolerance. In microglia, reactivation of SIX2 triggers an upregulation of FXYD2, which in turn helps attenuate neuroinflammation and protect dopaminergic neurons in models of Parkinson’s disease. Together, these findings highlight how FXYD2 serves diverse regulatory roles across different tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn summary, while the abstracts focus on FXYD2 and its influence on Na,K‑ATPase function across kidney, neural, and pancreatic tissues—as well as its involvement in anti‐inflammatory responses—the function of SORCS3‑AS1 is not addressed by these studies.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "D H Jones, M C Golding, K J Barr, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The mouse Na+-K+-ATPase gamma-subunit gene (Fxyd2) encodes three developmentally regulated transcripts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Physiol Genomics (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/physiolgenomics.2001.6.3.129"}], "href": "https://doi.org/10.1152/physiolgenomics.2001.6.3.129"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11526196"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11526196"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "D Holstead Jones, Tony Y Li, Elena Arystarkhova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Na,K-ATPase from mice lacking the gamma subunit (FXYD2) exhibits altered Na+ affinity and decreased thermal stability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M500697200"}], "href": "https://doi.org/10.1074/jbc.M500697200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15755730"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15755730"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kaarina Pihakaski-Maunsbach, Shigeki Tokonabe, Henrik Vorum, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The gamma-subunit of Na-K-ATPase is incorporated into plasma membranes of mouse IMCD3 cells in response to hypertonicity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00162.2004"}], "href": "https://doi.org/10.1152/ajprenal.00162.2004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15572522"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15572522"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Juan M Capasso, Christopher J Rivard, Tomas Berl "}, {"type": "b", "children": [{"type": "t", "text": "Silencing and overexpression of the gamma-subunit of Na-K-ATPase directly affect survival of IMCD3 cells in response to hypertonic stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00077.2006"}], "href": "https://doi.org/10.1152/ajprenal.00077.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16804105"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16804105"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Feng Wang, Bing Cai, Kai-Cheng Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FXYD2, a γ subunit of Na⁺, K⁺-ATPase, maintains persistent mechanical allodynia induced by inflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cr.2015.12"}], "href": "https://doi.org/10.1038/cr.2015.12"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25633594"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25633594"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Stéphanie Ventéo, Steeve Bourane, Ilana Méchaly, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of the Na,K-ATPase gamma-subunit FXYD2 by Runx1 and Ret signaling in normal and injured non-peptidergic nociceptive sensory neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0029852"}], "href": "https://doi.org/10.1371/journal.pone.0029852"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22253804"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22253804"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Elena Arystarkhova, Yi B Liu, Cynthia Salazar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hyperplasia of pancreatic beta cells and improved glucose tolerance in mice deficient in the FXYD2 subunit of Na,K-ATPase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.401190"}], "href": "https://doi.org/10.1074/jbc.M112.401190"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23344951"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23344951"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Xia-Yin Cao, Yi Liu, Jia-Shuo Kan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Microglial SIX2 suppresses lipopolysaccharide (LPS)-induced neuroinflammation by up-regulating FXYD2 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Res Bull (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.brainresbull.2024.110970"}], "href": "https://doi.org/10.1016/j.brainresbull.2024.110970"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38688414"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38688414"}]}]}]}