{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlthough the query requests a summary of TMEM200C, none of the provided abstracts mention TMEM200C. Instead, these studies focus on the pivotal role of alpha‑1,6‑fucosyltransferase (FUT8) in mediating core fucosylation of N‑glycans. FUT8‐dependent core fucosylation is shown to be essential for proper ligand–receptor interactions—such as those involving the epidermal growth factor receptor (EGFR), transforming growth factor‑β receptors, and vascular endothelial growth factor receptor‑2 (VEGFR‑2)—thereby modulating downstream signaling pathways that govern cell proliferation, differentiation, and tissue regeneration. In several experimental models, loss or reduction of FUT8 activity leads to marked defects in receptor phosphorylation, impaired cell–cell adhesion, and altered downstream cascades, which together contribute to phenotypes such as growth retardation, delayed liver regeneration, abnormal erythropoiesis, impaired immune cell development, and even structural changes underlying diseases like emphysema and psoriasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the central nervous system, FUT8 deficiency is associated with several behavioral and electrophysiological abnormalities. Animal studies indicate that lack of FUT8 impairs long-term potentiation in the hippocampus, leads to schizophrenia-like phenotypes with alterations in CaMKII phosphorylation and AMPA receptor dynamics, and ultimately disrupts adult neurogenesis and cognitive function. These findings underscore the importance of proper core fucosylation in maintaining neuronal signaling integrity and behavioral homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond receptor signaling and neural function, altered FUT8 expression is implicated in the progression of malignancies, chronic inflammatory conditions, and tissue fibrosis. Up‑regulation of FUT8 contributes to enhanced tumor cell invasion and metastasis in lung and liver cancers, in part by modifying the glycosylation of cell adhesion molecules and receptors. In immune cells, absence of core fucosylation hinders critical developmental transitions, such as the pro‑B to pre‑B cell transition, which further compromises immunoglobulin production. Structural studies provide insight into FUT8’s substrate specificity and dimerization, explaining its regulatory interactions with other glycosyltransferases such as ST6GAL1. Moreover, in models of chronic obstructive pulmonary disease, ulcerative colitis, and renal ischemia–reperfusion injury, aberrant FUT8 activity alters inflammatory signaling, highlighting its potential as a non‑invasive biomarker and therapeutic target in diverse pathological settings."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xiangchun Wang, Jianguo Gu, Hideyuki Ihara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Core fucosylation regulates epidermal growth factor receptor-mediated intracellular signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M510893200"}], "href": "https://doi.org/10.1074/jbc.M510893200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16316986"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16316986"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Wenzhe Li, Takatoshi Nakagawa, Nobuto Koyama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Down-regulation of trypsinogen expression is associated with growth retardation in alpha1,6-fucosyltransferase-deficient mice: attenuation of proteinase-activated receptor 2 activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Glycobiology (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/glycob/cwl023"}], "href": "https://doi.org/10.1093/glycob/cwl023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16861703"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16861703"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hitoshi Sasaki, Takanori Toda, Toru Furukawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "α-1,6-Fucosyltransferase (FUT8) inhibits hemoglobin production during differentiation of murine and K562 human erythroleukemia cells."}]}, {"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.M113.459594"}], "href": "https://doi.org/10.1074/jbc.M113.459594"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23609441"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23609441"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yuqin Wang, Tomohiko Fukuda, Tomoya Isaji, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of α1,6-fucosyltransferase suppressed liver regeneration: implication of core fucose in the regulation of growth factor receptor-mediated cellular signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep08264"}], "href": "https://doi.org/10.1038/srep08264"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25652335"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25652335"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Musin Kelel, Ruey-Bing Yang, Tsen-Fang Tsai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FUT8 Remodeling of EGFR Regulates Epidermal Keratinocyte Proliferation during Psoriasis Development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jid.2020.07.030"}], "href": "https://doi.org/10.1016/j.jid.2020.07.030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32888953"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32888953"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Tomohiko Fukuda, Hirokazu Hashimoto, Natsumi Okayasu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Alpha1,6-fucosyltransferase-deficient mice exhibit multiple behavioral abnormalities associated with a schizophrenia-like phenotype: importance of the balance between the dopamine and serotonin systems."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.172536"}], "href": "https://doi.org/10.1074/jbc.M110.172536"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21471224"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21471224"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Wei Gu, Tomohiko Fukuda, Tomoya Isaji, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of α1,6-Fucosyltransferase Decreases Hippocampal Long Term Potentiation: IMPLICATIONS FOR CORE FUCOSYLATION IN THE REGULATION OF AMPA RECEPTOR HETEROMERIZATION AND CELLULAR SIGNALING."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M114.579938"}], "href": "https://doi.org/10.1074/jbc.M114.579938"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25979332"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25979332"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Xu Lu, Dongmei Zhang, Hayato Shoji, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deficiency of α1,6-fucosyltransferase promotes neuroinflammation by increasing the sensitivity of glial cells to inflammatory mediators."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Gen Subj (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbagen.2018.12.008"}], "href": "https://doi.org/10.1016/j.bbagen.2018.12.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30572004"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30572004"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Hongfeng Guo, Qihang Sun, Xiaoli Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fucosyltransferase 8 regulates adult neurogenesis and cognition of mice by modulating the Itga6-PI3K/Akt signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci China Life Sci (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11427-023-2510-0"}], "href": "https://doi.org/10.1007/s11427-023-2510-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38523237"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38523237"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Wenzhe Li, Katsuhiko Ishihara, Takafumi Yokota, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reduced alpha4beta1 integrin/VCAM-1 interactions lead to impaired pre-B cell repopulation in alpha 1,6-fucosyltransferase deficient mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Glycobiology (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/glycob/cwm107"}], "href": "https://doi.org/10.1093/glycob/cwm107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17913729"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17913729"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Xiangchun Wang, Tomohiko Fukuda, Wenzhe Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Requirement of Fut8 for the expression of vascular endothelial growth factor receptor-2: a new mechanism for the emphysema-like changes observed in Fut8-deficient mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biochem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jb/mvp022"}], "href": "https://doi.org/10.1093/jb/mvp022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19179362"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19179362"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Valerie Vanhooren, Sylviane Dewaele, Makoto Kuro-O, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Alteration in N-glycomics during mouse aging: a role for FUT8."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging Cell (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1474-9726.2011.00749.x"}], "href": "https://doi.org/10.1111/j.1474-9726.2011.00749.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21951615"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21951615"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Koichiro Kamio, Takayuki Yoshida, Congxiao Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "α1,6-Fucosyltransferase (Fut8) is implicated in vulnerability to elastase-induced emphysema in mice and a possible non-invasive predictive marker for disease progression and exacerbations in chronic obstructive pulmonary disease (COPD)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2012.06.081"}], "href": "https://doi.org/10.1016/j.bbrc.2012.06.081"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22732410"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22732410"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Chien-Yu Chen, Yi-Hua Jan, Yi-Hsiu Juan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fucosyltransferase 8 as a functional regulator of nonsmall cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1220425110"}], "href": "https://doi.org/10.1073/pnas.1220425110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23267084"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23267084"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Guoling Huang, Zhi Li, Yuqing Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of core fucosylation in both ST6GAL1 and its substrate enhances glycoprotein sialylation in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BCJ20190789"}], "href": "https://doi.org/10.1042/BCJ20190789"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32141499"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32141499"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Michael A Järvå, Marija Dramicanin, James P Lingford, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis of substrate recognition and catalysis by fucosyltransferase 8."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA120.013291"}], "href": "https://doi.org/10.1074/jbc.RA120.013291"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32220931"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32220931"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Cheng Zhang, Qiong Wu, Huang Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Caveolin-1 upregulates Fut8 expression by activating the Wnt/β-catenin pathway to enhance HCC cell proliferative and invasive ability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Biol Int (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cbin.11426"}], "href": "https://doi.org/10.1002/cbin.11426"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32710651"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32710651"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Mengzhen Kuang, Hao Wu, Lan Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Up-regulation of FUT8 inhibits TGF-β1-induced activation of hepatic stellate cells during liver fibrogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Glycoconj J (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10719-021-09975-x"}], "href": "https://doi.org/10.1007/s10719-021-09975-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33608773"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33608773"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Gerard Cantero-Recasens, Carla Burballa, Yuki Ohkawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ulcerative colitis-associated gene FUT8 regulates the quantity and quality of secreted mucins."}]}, {"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.2205277119"}], "href": "https://doi.org/10.1073/pnas.2205277119"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36252012"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36252012"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Zhitong Li, Jiaojiao Hao, Longkai Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of FUT8 in renal tubules ameliorates ischemia-reperfusion injury-induced renal interstitial inflammation transition to fibrosis via the TLR3-NF-κB pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.202300623R"}], "href": "https://doi.org/10.1096/fj.202300623R"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37432656"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37432656"}]}]}]}