{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPikachurin is a highly conserved extracellular matrix protein that plays a critical role in organizing the photoreceptor ribbon synapse by binding to α‑dystroglycan. This interaction is calcium‑dependent and requires a specific steric conformation of its laminin globular domains, as well as proper post‑translational modifications of dystroglycan by enzymes such as Large and POMGnT1. These modifications ensure that dystroglycan attains the necessary glycosylation status to interact with pikachurin, anchoring it within the synaptic cleft."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDefective glycosylation of α‑dystroglycan, which occurs in congenital muscular dystrophies and is modeled in Large(myd) and POMGnT1‑deficient mice, markedly reduces the binding efficiency of pikachurin. This hypoglycosylation disrupts the precise localization of pikachurin at the photoreceptor synapse, thereby impairing the structural integrity of the synaptic interface. Overexpression of glycosylation‑enhancing factors can partially restore the interaction, underscoring the necessity of normal glycosylation for pikachurin’s synaptic function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, functional studies in pikachurin null‑mutant mice reveal that this protein is indispensable for proper signal transmission between photoreceptors and ON bipolar cells. The absence of pikachurin leads to anomalous photopic electroretinographic responses during light adaptation, demonstrating a direct link between the molecular organization of the synapse and retinal physiological function. These findings collectively emphasize that pikachurin is essential not only for the molecular assembly of the synaptic interface but also for the functional adaptation of the visual system."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Motoi Kanagawa, Yoshihiro Omori, Shigeru Sato, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Post-translational maturation of dystroglycan is necessary for pikachurin binding and ribbon synaptic localization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.116343"}], "href": "https://doi.org/10.1074/jbc.M110.116343"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20682766"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20682766"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jianzhong Han, Ellen Townes-Anderson "}, {"type": "b", "children": [{"type": "t", "text": "Cell specific post-translational processing of pikachurin, a protein involved in retinal synaptogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0050552"}], "href": "https://doi.org/10.1371/journal.pone.0050552"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23226524"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23226524"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Huaiyu Hu, Jing Li, Zhen Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pikachurin interaction with dystroglycan is diminished by defective O-mannosyl glycosylation in congenital muscular dystrophy models and rescued by LARGE overexpression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurosci Lett (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neulet.2010.11.056"}], "href": "https://doi.org/10.1016/j.neulet.2010.11.056"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21129441"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21129441"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Masatoshi Nagaya, Shinji Ueno, Taro Kominami, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pikachurin Protein Required for Increase of Cone Electroretinogram B-Wave during Light Adaptation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0128921"}], "href": "https://doi.org/10.1371/journal.pone.0128921"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26091521"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26091521"}]}]}]}