{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Junctional adhesion molecule 3 (JAM3), also known as JAM‐C, is a multifunctional immunoglobulin superfamily protein that plays diverse roles in vascular homeostasis, inflammation, cell–cell adhesion, and tissue remodeling. JAM3 functions as a heteroreceptor on platelets by directly interacting with the leukocyte β2‐integrin Mac‐1, thereby promoting leukocyte–platelet adhesion and contributing to inflammatory vascular diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Moreover, JAM3 forms heterotypic complexes with JAM2 to mediate adhesive interactions with T lymphocytes, with its cell‐surface levels increasing upon lymphocyte activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n On endothelial cells, JAM3 localizes at intercellular junctions and is critical for neutrophil transmigration in a Mac‐1–dependent manner; its regulated expression and redistribution under inflammatory conditions underpin its role in controlling vascular permeability and leukocyte recruitment"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In addition, reduced or mutated JAM3 impairs the integrity of cerebrovascular barriers, as evidenced by severe hemorrhagic brain destruction and congenital cataracts in patients harboring JAM3 mutations."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Furthermore, under conditions of acute inflammation such as pancreatitis, down‐regulation of pancreatic JAM3 is associated with increased reverse transmigration of neutrophils and exacerbated lung injury."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond inflammation and vascular integrity, JAM3 is essential for proper cellular polarization during spermatogenesis; it facilitates the differentiation of round spermatids into fully polarized spermatozoa via its role in assembling cell polarity complexes and interacting with partners such as CAR, thereby impacting male fertility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In addition, homophilic interactions of JAM3—mediated by its membrane‐distal immunoglobulin domain—promote tumor cell adhesion to endothelial cells, a process that may contribute to cancer cell extravasation and metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the broad biological functions of JAM3 in regulating immune cell trafficking, maintaining endothelial barrier integrity, and ensuring proper cell polarity in reproductive and malignant settings.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sentot Santoso, Ulrich J H Sachs, Hartmut Kroll, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The junctional adhesion molecule 3 (JAM-3) on human platelets is a counterreceptor for the leukocyte integrin Mac-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20020267"}], "href": "https://doi.org/10.1084/jem.20020267"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12208882"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12208882"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "M P Arrate, J M Rodriguez, T M Tran, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cloning of human junctional adhesion molecule 3 (JAM3) and its identification as the JAM2 counter-receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M105972200"}], "href": "https://doi.org/10.1074/jbc.M105972200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11590146"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11590146"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Triantafyllos Chavakis, Tanja Keiper, Rachel Matz-Westphal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The junctional adhesion molecule-C promotes neutrophil transendothelial migration in vitro and in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M404676200"}], "href": "https://doi.org/10.1074/jbc.M404676200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15485832"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15485832"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Tanja Keiper, Nadia Al-Fakhri, Emmanouil Chavakis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The role of junctional adhesion molecule-C (JAM-C) in oxidized LDL-mediated leukocyte recruitment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.05-4196fje"}], "href": "https://doi.org/10.1096/fj.05-4196fje"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16195363"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16195363"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ganeshwaran H Mochida, Vijay S Ganesh, Jillian M Felie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A homozygous mutation in the tight-junction protein JAM3 causes hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2010.10.026"}], "href": "https://doi.org/10.1016/j.ajhg.2010.10.026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21109224"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21109224"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Deqing Wu, Yue Zeng, Yuting Fan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reverse-migrated neutrophils regulated by JAM-C are involved in acute pancreatitis-associated lung injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep20545"}], "href": "https://doi.org/10.1038/srep20545"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26841848"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26841848"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Georgia Gliki, Klaus Ebnet, Michel Aurrand-Lions, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Spermatid differentiation requires the assembly of a cell polarity complex downstream of junctional adhesion molecule-C."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature02877"}], "href": "https://doi.org/10.1038/nature02877"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15372036"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15372036"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Sentot Santoso, Valeria V Orlova, Kaimei Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The homophilic binding of junctional adhesion molecule-C mediates tumor cell-endothelial cell interactions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M505059200"}], "href": "https://doi.org/10.1074/jbc.M505059200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16118203"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16118203"}]}]}]}