{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSTX3 is a key component of the membrane‐fusion and vesicular trafficking machinery that regulates apical exocytosis in polarized epithelial cells. Loss‐of‐function of STX3 impairs fusion of apical vesicles—leading, for example, to severe congenital enteropathies such as variant microvillus inclusion disease—and disrupts the recycling of critical apical proteins such as CFTR. Studies in enterocytes and epithelial cell models have shown that STX3, working in conjunction with factors such as myosin Vb, Rab11a, and Munc18b, directs apical cargo trafficking, thereby establishing and maintaining epithelial polarity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n\nIn addition to its role in epithelial cells, STX3 participates in specialized secretory pathways in immune and vascular systems. In mast cells, STX3 is essential for the exocytosis of newly synthesized chemokines, thereby modulating inflammatory responses. In endothelial cells, STX3 has been implicated in the regulated secretion of von Willebrand factor from Weibel–Palade bodies and also appears to contribute to the trafficking of integrins that influence cell adhesion and migration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": "\n\nSTX3 also plays diverse roles in the control of viral life cycles, tumorigenesis, and developmental disorders. In the context of viral infection, STX3 contributes to the envelopment and egress of human cytomegalovirus, and its down‐regulation by specific viral microRNAs correlates with reduced viral replication. In cancer models, especially in breast and esophageal carcinomas, STX3 is frequently up‐regulated and acts as an oncogenic driver—partly through its interactions that promote PTEN degradation and subsequent activation of the PI3K–Akt–mTOR signaling pathway—as well as by functioning as a nuclear modulator via a soluble isoform that interacts with transcription factors. Moreover, germline mutations or loss‐of‐function variants in STX3 have been implicated in congenital disorders, including syndromic microvillus inclusion disease with retinal dystrophy and congenital cataract, while biochemical studies and protein‐engineering approaches have provided insights into its structure–function relationships. Intriguingly, extracellular release of STX3 from dying keratinocytes under oxidative stress conditions can inhibit apoptotic cascades, thereby promoting cell survival."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "19"}]}, {"type": "t", "text": "\n\nIn pancreatic β‐cells, a related isoform (SYN-3) has been observed in secretory granules, although its precise role in insulin exocytosis remains to be elucidated."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Maria Kauppi, Gerd Wohlfahrt, Vesa M Olkkonen "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of the Munc18b-syntaxin binding interface. 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"}, {"type": "b", "children": [{"type": "t", "text": "Munc18b regulates core SNARE complex assembly and constitutive exocytosis by interacting with the N-peptide and the closed-conformation C-terminus of syntaxin 3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20100145"}], "href": "https://doi.org/10.1042/BJ20100145"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20695848"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20695848"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Anne Collaco, Jai Marathe, Hannes Kohnke, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "STX3 represses the stability of the tumor suppressor PTEN to activate the PI3K-Akt-mTOR signaling and promotes the growth of breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Basis Dis (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbadis.2018.01.031"}], "href": "https://doi.org/10.1016/j.bbadis.2018.01.031"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29408595"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29408595"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Adrian J Giovannone, Christine Winterstein, Pallavi Bhattaram, et al. 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