{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LYPD6 is a member of the Ly6/uPAR protein superfamily characterized by a “three‐finger” LU domain that endows it with multifunctional signaling properties. Multiple studies have shown that LYPD6 acts as a positive modulator of canonical Wnt/β‐catenin signaling by promoting the phosphorylation of the Wnt co‐receptor LRP6 within membrane raft domains, thereby enhancing downstream pathway activity during embryonic patterning and tissue homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In parallel, LYPD6 modulates cholinergic neurotransmission through interactions with nicotinic acetylcholine receptors (nAChRs). On one hand, neuronal overexpression of LYPD6 has been associated with enhanced Ca²⁺ influx via heteromeric nAChRs, while on the other, soluble forms of LYPD6 can attenuate nicotine‐evoked intracellular signaling responses—together suggesting a complex role in fine‐tuning cholinergic activity that may impact behavior, including anxiety."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": " Furthermore, differential LYPD6 expression in subpopulations of cortical interneurons—being enriched in somatostatin‐expressing cells and absent in parvalbumin neurons—points to a role in the regulation of inhibitory circuitry and experience‐dependent plasticity in the adult visual cortex."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Additional reports have linked aberrant LYPD6 gene dosage with neurodevelopmental disturbances, as duplications encompassing the LYPD6 locus have been observed in subjects with global developmental delay."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Structural studies further reveal that the LU domain of LYPD6 exhibits marked conformational plasticity—likely a prerequisite for its selective interactions with both Wnt coreceptors and nAChRs"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "—and analyses in heterologous systems have even suggested roles in modulating transcriptional activities."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Collectively, these findings highlight LYPD6 as a versatile modulator at the interplay of Wnt and cholinergic signaling pathways, with implications for neural circuit refinement, cognitive function, and potential therapeutic targeting.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Günes Özhan, Erdinc Sezgin, Daniel Wehner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lypd6 enhances Wnt/β-catenin signaling by promoting Lrp6 phosphorylation in raft plasma membrane domains."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2013.07.020"}], "href": "https://doi.org/10.1016/j.devcel.2013.07.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23987510"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23987510"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yuguang Zhao, Jingshan Ren, Weixian Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure of the Wnt signaling enhancer LYPD6 and its interactions with the Wnt coreceptor LRP6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1873-3468.13212"}], "href": "https://doi.org/10.1002/1873-3468.13212"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30069874"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30069874"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Vikas Singh, Sahana Holla, Subbaraya G Ramachandra, et al. "}, {"type": "b", "children": [{"type": "t", "text": "WNT-inflammasome signaling mediates NOD2-induced development of acute arthritis in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1402498"}], "href": "https://doi.org/10.4049/jimmunol.1402498"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25717000"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25717000"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Martin Darvas, Marco Morsch, Ildiko Racz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Modulation of the Ca2+ conductance of nicotinic acetylcholine receptors by Lypd6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Neuropsychopharmacol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.euroneuro.2009.03.007"}], "href": "https://doi.org/10.1016/j.euroneuro.2009.03.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19403274"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19403274"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Maria Arvaniti, Majbrit M Jensen, Neeraj Soni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional interaction between Lypd6 and nicotinic acetylcholine receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurochem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jnc.13718"}], "href": "https://doi.org/10.1111/jnc.13718"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27344019"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27344019"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Maria Arvaniti, Filip S Polli, Kristi A Kohlmeier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of Lypd6 leads to reduced anxiety-like behaviour and enhanced responses to nicotine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Prog Neuropsychopharmacol Biol Psychiatry (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.pnpbp.2017.11.025"}], "href": "https://doi.org/10.1016/j.pnpbp.2017.11.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29195920"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29195920"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Michael P Demars, Hirofumi Morishita "}, {"type": "b", "children": [{"type": "t", "text": "Cortical parvalbumin and somatostatin GABA neurons express distinct endogenous modulators of nicotinic acetylcholine receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Brain (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13041-014-0075-9"}], "href": "https://doi.org/10.1186/s13041-014-0075-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25359633"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25359633"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Masato Sadahiro, Michael P Demars, Poromendro Burman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of Somatostatin Interneurons by Nicotinic Modulator Lypd6 Enhances Plasticity and Functional Recovery in the Adult Mouse Visual Cortex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.1373-19.2020"}], "href": "https://doi.org/10.1523/JNEUROSCI.1373-19.2020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32467358"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32467358"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Xuelian He, Yufeng Huang, Sukun Luo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Phenotypic and genotypic analysis of a girl carrying a 2q22.3 microduplication encompassing the MBD5 gene]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Zhonghua Yi Xue Yi Chuan Xue Za Zhi (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3760/cma.j.issn.1003-9406.2019.06.024"}], "href": "https://doi.org/10.3760/cma.j.issn.1003-9406.2019.06.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31055822"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31055822"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Brian H Y Chung, Sureni Mullegama, Christian R Marshall, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Severe intellectual disability and autistic features associated with microduplication 2q23.1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ejhg.2011.199"}], "href": "https://doi.org/10.1038/ejhg.2011.199"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22085900"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22085900"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Alexander S Paramonov, Milita V Kocharovskaya, Andrey V Tsarev, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural Diversity and Dynamics of Human Three-Finger Proteins Acting on Nicotinic Acetylcholine Receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms21197280"}], "href": "https://doi.org/10.3390/ijms21197280"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33019770"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33019770"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Yifeng Zhang, Qingyu Lang, Jie Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification and characterization of human LYPD6, a new member of the Ly-6 superfamily."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Rep (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11033-009-9663-7"}], "href": "https://doi.org/10.1007/s11033-009-9663-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19653121"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19653121"}]}]}]}