{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nIn pancreatic β‐cells, precise regulation of exocytosis is essential for stimulus‐secretion coupling. Detailed electrophysiological studies have shown that distinct Munc18 isoforms, through differential phosphorylation and subcellular localization, modulate the Ca²⁺ sensitivity of insulin secretion, thereby fine‐tuning hormonal release."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n \nIn airway epithelial cells and mast cells, tightly controlled regulated exocytosis underlies both mucin secretion and immune mediator release. Here, Munc18b and the coordinated assembly of SNARE complexes—facilitated by critical C‐terminal domains and SNARE‐like peptides—ensure that vesicle fusion occurs only upon appropriate stimulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n \nStudies focusing on mast cells and platelets further reveal that the Munc18‐2 isoform is uniquely indispensable for regulated degranulation. Loss of Munc18‐2 leads to severely impaired membrane fusion events, correlating with markedly reduced anaphylactic responses and defective platelet granule release, thereby supporting a nonredundant role in these secretory processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n \nThree‐dimensional intestinal organoid models, which recapitulate the polarized nature of absorptive cells, have demonstrated that perturbations in apical vesicular transport can lead to marked defects in epithelial function. These findings underscore the broader physiological impact of regulated exocytosis in maintaining tissue homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n \nIn the reproductive system, investigations in testicular Sertoli cells indicate that proteins such as STXBP2 mediate key cell–cell interactions. By interacting with connexin 43, STXBP2 regulates Sertoli cell migration and supports germ cell survival, highlighting an essential role for the vesicular transport machinery in testicular function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n \nMoreover, in the context of systemic infection, platelet studies have illuminated how STING activation can drive granule secretion by promoting SNARE complex assembly. This cascade plays a pivotal role in the pathogenesis of sepsis, where uncontrolled exocytosis can lead to thrombosis and coagulopathy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n \nCollectively, these diverse investigations delineate the fundamental mechanisms governing regulated exocytosis—from hormonal secretion and mucin release to immune and hemostatic responses—and emphasize the critical roles played by specific Munc18 isoforms, SNARE domains, and accessory proteins. Although LINC01589 is not directly examined in any of these reports, its status as a long intergenic noncoding RNA suggests that it may function as an additional regulatory layer—potentially modulating the transcription or post‐translational activity of these key exocytic factors. Future studies are warranted to determine whether LINC01589 interfaces with this exocytic machinery to influence cellular homeostasis across pulmonary, endocrine, immune, and reproductive systems.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Slavena A Mandic, Masa Skelin, Jenny U Johansson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Munc18-1 and Munc18-2 proteins modulate beta-cell Ca2+ sensitivity and kinetics of insulin exocytosis differently."}]}, {"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.M111.235366"}], "href": "https://doi.org/10.1074/jbc.M111.235366"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21690086"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21690086"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kyubo Kim, Youlia M Petrova, Brenton L Scott, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Munc18b is an essential gene in mice whose expression is limiting for secretion by airway epithelial and mast cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20120057"}], "href": "https://doi.org/10.1042/BJ20120057"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22694344"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22694344"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Haijia Yu, Chong Shen, Yinghui Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SNARE zippering requires activation by SNARE-like peptides in Sec1/Munc18 proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1802645115"}], "href": "https://doi.org/10.1073/pnas.1802645115"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30127032"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30127032"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Berenice A Gutierrez, Miguel A Chavez, Alejandro I Rodarte, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Munc18-2, but not Munc18-1 or Munc18-3, controls compound and single-vesicle-regulated exocytosis in mast cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA118.002455"}], "href": "https://doi.org/10.1074/jbc.RA118.002455"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29599294"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29599294"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Eduardo I Cardenas, Ricardo Gonzalez, Keegan Breaux, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Munc18-2, but not Munc18-1 or Munc18-3, regulates platelet exocytosis, hemostasis, and thrombosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA118.006922"}], "href": "https://doi.org/10.1074/jbc.RA118.006922"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30696774"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30696774"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Mohammed H Mosa, Ophélie Nicolle, Sophia Maschalidi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dynamic Formation of Microvillus Inclusions During Enterocyte Differentiation in "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "Munc18-2"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": "-Deficient Intestinal Organoids."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Gastroenterol Hepatol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jcmgh.2018.08.001"}], "href": "https://doi.org/10.1016/j.jcmgh.2018.08.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30364784"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30364784"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yibo Wu, Cong Shen, Tiantian Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Syntaxin binding protein 2 in sertoli cells regulates spermatogonial stem cell maintenance through directly interacting with connexin 43 in the testes of neonatal mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Rep (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11033-022-07564-1"}], "href": "https://doi.org/10.1007/s11033-022-07564-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35604625"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35604625"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Mina Yang, Haojie Jiang, Chen Ding, et al. "}, {"type": "b", "children": [{"type": "t", "text": "STING activation in platelets aggravates septic thrombosis by enhancing platelet activation and granule secretion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunity (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.immuni.2023.02.015"}], "href": "https://doi.org/10.1016/j.immuni.2023.02.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36944334"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36944334"}]}]}]}