{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTorsinA, the protein encoded by TOR1A, is a member of the AAA+ ATPase family that predominantly resides within the lumen of the endoplasmic reticulum and the nuclear envelope. In these locales, torsinA normally participates in controlling the architecture and dynamics of the nuclear envelope by interacting with key activators such as LAP1, LULL1, and nesprin family members. Such interactions appear to be critical for proper assembly of membrane‐associated complexes and for maintaining the connectivity between the nucleus and the cytoskeleton, while subtle structural features––including redox‐sensitive sensor motifs––help modulate its ATPase activity and oligomerization state."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its structural roles, torsinA functions as an endoplasmic reticulum chaperone that facilitates proper protein processing and trafficking through the secretory pathway. It is implicated in endoplasmic reticulum–associated degradation (ERAD) by interacting with factors that help clear misfolded proteins and by modulating the processing of diverse membrane proteins—including the dopamine transporter and various G protein–coupled receptors. Loss-of-function mutations in TOR1A, such as the common ΔE deletion, disrupt these processes, leading to protein mislocalization, aggregation, and enhanced cellular sensitivity to ER stress."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in maintaining ER and nuclear envelope integrity, torsinA is central to neuronal function. It influences the trafficking and cell-surface expression of key neurotransmitter transporters and receptors, thereby contributing to the balance between dopaminergic and cholinergic signaling in motor circuits. Aberrant torsinA function, caused by DYT1-associated mutations, results in altered synaptic plasticity and dysfunctional neural circuit integration that likely underlie the motor deficits observed in dystonia patients and animal models."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Rose E Goodchild, William T Dauer "}, {"type": "b", "children": [{"type": "t", "text": "Mislocalization to the nuclear envelope: an effect of the dystonia-causing torsinA mutation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0304375101"}], "href": "https://doi.org/10.1073/pnas.0304375101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14711988"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14711988"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Rose E Goodchild, William T Dauer "}, {"type": "b", "children": [{"type": "t", "text": "The AAA+ protein torsinA interacts with a conserved domain present in LAP1 and a novel ER protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200411026"}], "href": "https://doi.org/10.1083/jcb.200411026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15767459"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15767459"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Flávia C Nery, Juan Zeng, Brian P Niland, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TorsinA binds the KASH domain of nesprins and participates in linkage between nuclear envelope and cytoskeleton."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.029454"}], "href": "https://doi.org/10.1242/jcs.029454"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18827015"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18827015"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jeffrey W Hewett, Bakhos Tannous, Brian P Niland, et al. 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