{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The DNM3 gene has emerged as a multifaceted locus whose products play diverse roles in both metabolic regulation and cell signaling. Genome‐wide association studies have identified a DNM3‐PIGC locus that contributes to body fat distribution independent of overall adiposity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the nervous system, the dynamin‐3 protein is differentially localized and functionally specialized. Early studies showed that dynamin‐3 forms a physical link with the postsynaptic adaptor Homer to position endocytic zones in close proximity to the postsynaptic density, thereby contributing to the rapid, spatially controlled recycling of receptors at synapses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, although dynamin‐3 was initially thought to be confined to postsynaptic compartments, subsequent work demonstrated that its loss exacerbates synaptic vesicle recycling defects in the absence of dynamin‐1, indicating that dynamin‐3 also has a critical presynaptic role"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "and is involved in dendritic spine morphogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to the protein‐coding functions of DNM3, the locus gives rise to a long noncoding transcript (DNM3 opposite strand, or DNM3os) that encodes a unique microRNA cluster comprising, among others, miR‐199a and miR‐214. Expression of these miRNAs is tightly regulated during cell differentiation and in disease contexts. For example, in ovarian cancer stem cells the coordinated regulation of miR‐199a/214 from the DNM3os transcript is controlled by Twist1 and modulates the IKKβ/NF‐κB and PTEN/AKT pathways that influence “stemness” and cellular differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Complementary observations have revealed that miR‐199a is transcribed antisense to DNM3 and functions as a tumor suppressor by targeting proteins that promote cellular invasion and metastasis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", while elevated levels of miR‐199a‐5p—which is also derived from the dynamin‐3 locus—have been implicated in regulating myogenesis through suppression of WNT‐signaling factors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Furthermore, the DNM3os‐derived miR‐214 plays a central role in controlling fibrogenic responses by downregulating connective tissue growth factor (CCN2) in hepatic stellate cells, thereby modulating extracellular matrix deposition in liver fibrosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, the DNM3 locus exemplifies a “dual‐function” gene: its protein product, dynamin‐3, is essential for the precise spatial regulation of synaptic vesicle recycling and dendritic spine morphology, while its opposite strand transcript produces a microRNA cluster that fine‐tunes key signaling networks involved in cell differentiation, proliferation, and fibrogenesis. Collectively, these findings underscore the complex regulatory roles of DNM3 in both neuronal function and pathological processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Iris M Heid, Anne U Jackson, Joshua C Randall, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.685"}], "href": "https://doi.org/10.1038/ng.685"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20935629"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20935629"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jiuyi Lu, Thomas D Helton, Thomas A Blanpied, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Overlapping role of dynamin isoforms in synaptic vesicle endocytosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2011.04.031"}], "href": "https://doi.org/10.1016/j.neuron.2011.04.031"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21689597"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21689597"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Noah W Gray, Lawrence Fourgeaud, Bing Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dynamin 3 is a component of the postsynapse, where it interacts with mGluR5 and Homer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0960-9822(03)00136-2"}], "href": "https://doi.org/10.1016/s0960-9822(03"}, {"type": "t", "text": "00136-2) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12646135"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12646135"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "G Yin, R Chen, A B Alvero, et al. 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