{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n JP‐45, encoded by the JSRP1 gene, is an integral membrane protein localized at the junctional face of the sarcoplasmic reticulum in skeletal muscle. It plays a critical modulatory role in excitation–contraction coupling through its direct interactions with the voltage‐dependent Ca²⁺ channel (Ca_v1.1) and the Ca²⁺‐buffering protein calsequestrin. JP‐45 binds to distinct regions of Ca_v1.1—including the I–II loop and C‐terminal domains—thereby influencing charge movement and the permeability of the dihydropyridine receptor during muscle depolarization (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Genetic ablation or polymorphic variants of JSRP1/JP‐45 have been shown to decrease the functional expression and sensitivity of Ca_v1.1, resulting in excitation–contraction uncoupling and, ultimately, reduced muscle force generation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Conversely, in certain contexts the modulation by JP‐45 appears to have a protective effect; for example, its absence or altered function may counterbalance hypersensitivities in patients predisposed to conditions such as malignant hyperthermia. Further, detailed analyses in cellular models have demonstrated that both overexpression and depletion of JP‐45 lead to significant alterations in Ca²⁺ release properties, underscoring its role as a key regulator of the excitation–contraction machinery."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ayuk A Anderson, Susan Treves, Donatella Biral, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The novel skeletal muscle sarcoplasmic reticulum JP-45 protein. Molecular cloning, tissue distribution, developmental expression, and interaction with alpha 1.1 subunit of the voltage-gated calcium channel."}]}, {"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.M305016200"}], "href": "https://doi.org/10.1074/jbc.M305016200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12871958"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12871958"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ayuk A Anderson, Xavier Altafaj, Zhenlin Zheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The junctional SR protein JP-45 affects the functional expression of the voltage-dependent Ca2+ channel Cav1.1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.02935"}], "href": "https://doi.org/10.1242/jcs.02935"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16638807"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16638807"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Osvaldo Delbono, Jinyu Xia, Susan Treves, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of skeletal muscle strength by ablation of the sarcoplasmic reticulum protein JP45."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0707389104"}], "href": "https://doi.org/10.1073/pnas.0707389104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18077436"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18077436"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Toshimichi Yasuda, Osvaldo Delbono, Zhong-Min Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "JP-45/JSRP1 variants affect skeletal muscle excitation-contraction coupling by decreasing the sensitivity of the dihydropyridine receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.22209"}], "href": "https://doi.org/10.1002/humu.22209"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22927026"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22927026"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "E Gouadon, R P Schuhmeier, D Ursu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A possible role of the junctional face protein JP-45 in modulating Ca2+ release in skeletal muscle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Physiol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1113/jphysiol.2005.104406"}], "href": "https://doi.org/10.1113/jphysiol.2005.104406"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16423849"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16423849"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Osvaldo Delbono, Maria Laura Messi, Zhong-Min Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endogenously determined restriction of food intake overcomes excitation-contraction uncoupling in JP45KO mice with aging."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Gerontol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.exger.2012.01.004"}], "href": "https://doi.org/10.1016/j.exger.2012.01.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22297108"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22297108"}]}]}]}