{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nCollagen XIII is a multifunctional transmembrane protein that plays a pivotal role in orchestrating the formation and maturation of neuromuscular junctions (NMJs). It exists both as a membrane-bound protein and in a shed, soluble form, with its ectodomain promoting the clustering of acetylcholine receptors and ensuring appropriate adhesion between nerve terminals and the muscle surface. In collagen XIII–deficient mouse models, disruptions in both presynaptic neurotransmitter release and postsynaptic receptor maturation have been observed, resulting in compromised synaptic function and muscle weakness."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n \nDissection of its molecular architecture has revealed that collagen XIII contains a short intracellular segment, a single membrane-spanning region, and an extensive extracellular ectodomain characterized by distinct coiled-coil regions. These oligomerization domains are essential for proper chain association and protein folding, thereby ensuring the stability and functional integrity of the molecule."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n\nBeyond its critical roles at the NMJ, collagen XIII is also implicated in broader tissue homeostasis. In the renal cortex—a key site in Alport syndrome—it is aberrantly expressed in endothelial cells, where it mediates the selective recruitment of integrin‐positive monocytes, contributing to inflammatory fibrosis. Furthermore, mutations in COL13A1, the gene encoding collagen XIII, are associated with congenital myasthenic syndrome type 19, a condition marked by muscle weakness, craniofacial malformations, and a decline in bone mass with aging, while overexpression of mutant collagen XIII disrupts fetal cardiac function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Anne Latvanlehto, Michael A Fox, Raija Sormunen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Muscle-derived collagen XIII regulates maturation of the skeletal neuromuscular junction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.5518-09.2010"}], "href": "https://doi.org/10.1523/JNEUROSCI.5518-09.2010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20844119"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20844119"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Zarin Zainul, Anne Heikkinen, Hennariikka Koivisto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Collagen XIII Is Required for Neuromuscular Synapse Regeneration and Functional Recovery after Peripheral Nerve Injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.3119-17.2018"}], "href": "https://doi.org/10.1523/JNEUROSCI.3119-17.2018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29626165"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29626165"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Heli Härönen, Zarin Zainul, Nikolay Naumenko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Correct expression and localization of collagen XIII are crucial for the normal formation and function of the neuromuscular system."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Neurosci (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/ejn.14346"}], "href": "https://doi.org/10.1111/ejn.14346"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30667565"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30667565"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Anne Latvanlehto, Anne Snellman, Hongmin Tu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Type XIII collagen and some other transmembrane collagens contain two separate coiled-coil motifs, which may function as independent oligomerization domains."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M305974200"}], "href": "https://doi.org/10.1074/jbc.M305974200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12832406"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12832406"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jameel Dennis, Daniel T Meehan, Duane Delimont, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Collagen XIII induced in vascular endothelium mediates alpha1beta1 integrin-dependent transmigration of monocytes in renal fibrosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2353/ajpath.2010.100017"}], "href": "https://doi.org/10.2353/ajpath.2010.100017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20864678"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20864678"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jenni Tahkola, Juha Räsänen, Malin Sund, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cardiac dysfunction in transgenic mouse fetuses overexpressing shortened type XIII collagen."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Tissue Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00441-008-0617-5"}], "href": "https://doi.org/10.1007/s00441-008-0617-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18481090"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18481090"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "A V Kemppainen, M A Finnilä, A Heikkinen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The CMS19 disease model specifies a pivotal role for collagen XIII in bone homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-022-09653-4"}], "href": "https://doi.org/10.1038/s41598-022-09653-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35393492"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35393492"}]}]}]}