{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMDGA1 is a unique, glycosylphosphatidylinositol (GPI)‐anchored immunoglobulin superfamily protein that plays vital roles in proper forebrain development. It is expressed in a layer‐ and area‐selective manner in the neocortex, where it is essential for the radial migration and laminar positioning of superficial projection neurons. Loss-of-function studies have demonstrated that reducing MDGA1 expression disrupts the migration of layer II/III neurons, delaying their arrival into the appropriate cortical plate and altering cortical lamination patterns."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in neuronal migration, MDGA1 is increasingly recognized as a critical modulator of synaptic function. In hippocampal circuits, for instance, MDGA1 modulates synaptic organization by selectively suppressing inhibitory synapse formation and transmission—particularly at perisomatic and distal dendritic compartments of CA1 pyramidal neurons. Mechanistically, its MAM domain interacts with key synaptic partners such as the amyloid precursor protein (APP), and its proteolytic processing by BACE1 influences synaptic integrity. These perturbations in inhibitory balance are associated with altered neurotransmitter metabolism, impaired long-term potentiation, and consequent deficits in learning and behaviors such as prepulse inhibition."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast to the extensive roles of MDGA1 in neurodevelopment and synaptic modulation, recent studies have implicated ZNF280A—a distinct member of the zinc finger protein family—in tumorigenic processes. In lung adenocarcinoma (LUAD), ZNF280A acts as a tumor driver, where its overexpression correlates with higher tumor grade, advanced pathological stage, increased lymphatic metastasis, and poorer patient survival. Experimental loss-of-function approaches reduce malignant behaviors by impairing cell proliferation, migration, and survival, with EIF3C identified as a potential downstream effector. Moreover, emerging evidence also suggests that ZNF280A contributes to the progression of bladder cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Akihide Takeuchi, Dennis D M O'Leary "}, {"type": "b", "children": [{"type": "t", "text": "Radial migration of superficial layer cortical neurons controlled by novel Ig cell adhesion molecule MDGA1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.4935-05.2006"}], "href": "https://doi.org/10.1523/JNEUROSCI.4935-05.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16641224"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16641224"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Akihide Takeuchi, Tadashi Hamasaki, E David Litwack, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel IgCAM, MDGA1, expressed in unique cortical area- and layer-specific patterns and transiently by distinct forebrain populations of Cajal-Retzius neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cereb Cortex (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/cercor/bhl064"}], "href": "https://doi.org/10.1093/cercor/bhl064"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16959869"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16959869"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Takao Ishikawa, Naoya Gotoh, Chiaki Murayama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IgSF molecule MDGA1 is involved in radial migration and positioning of a subset of cortical upper-layer neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Dyn (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/dvdy.22496"}], "href": "https://doi.org/10.1002/dvdy.22496"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21104742"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21104742"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Steven A Connor, Ina Ammendrup-Johnsen, Yasushi Kishimoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of Synapse Repressor MDGA1 Enhances Perisomatic Inhibition, Confers Resistance to Network Excitation, and Impairs Cognitive Function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2017.11.109"}], "href": "https://doi.org/10.1016/j.celrep.2017.11.109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29281813"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29281813"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Md Razib Hossain, Mostofa Jamal, Yu Tanoue, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MDGA1-deficiency attenuates prepulse inhibition with alterations of dopamine and serotonin metabolism: An ex vivo HPLC-ECD analysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurosci Lett (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neulet.2019.134677"}], "href": "https://doi.org/10.1016/j.neulet.2019.134677"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31812551"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31812551"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jasenka Rudan Njavro, Jakob Klotz, Bastian Dislich, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mouse brain proteomics establishes MDGA1 and CACHD1 as in vivo substrates of the Alzheimer protease BACE1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.201902347R"}], "href": "https://doi.org/10.1096/fj.201902347R"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31908000"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31908000"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jinhu Kim, Seungjoon Kim, Hyeonho Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MDGA1 negatively regulates amyloid precursor protein-mediated synapse inhibition in the hippocampus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.2115326119"}], "href": "https://doi.org/10.1073/pnas.2115326119"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35074912"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35074912"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Hongsheng Liu, Yingzhi Qin, Na Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZNF280A promotes lung adenocarcinoma development by regulating the expression of EIF3C."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-020-03309-9"}], "href": "https://doi.org/10.1038/s41419-020-03309-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33414445"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33414445"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Long He, Xialu Wang, Peng Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of ZNF280A inhibits cell proliferation and promotes cell apoptosis of bladder cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Histol Histopathol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.14670/HH-18-640"}], "href": "https://doi.org/10.14670/HH-18-640"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37345848"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37345848"}]}]}]}