{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Members of the Ly6/uPAR “three‐finger” protein family—including the secreted SLURP proteins and the glycosylphosphatidylinositol (GPI)‐anchored Lynx proteins—play important neuromodulatory roles by interacting with nicotinic acetylcholine receptors (nAChRs) in both the central nervous system and peripheral tissues. For example, secreted SLURP proteins regulate cell growth, differentiation, and inflammatory responses in epithelial cells by modulating α7‐nAChR signaling via non‐channel “metabotropic” pathways, while Lynx1, predominantly associated with cell membranes, influences nAChR properties by modifying receptor activation, desensitization, and even subunit assembly. (1,2,3,4)"}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the epidermis, keratinocytes normally express both Lynx1 and SLURP2; however, despite reports of a hybrid transcript containing sequences from both genes (termed “LYNX1‐SLURP2”), detailed expression analyses have demonstrated that keratinocytes do not produce the fusion protein but rather express Lynx1 and SLURP2 as separate entities. In these cells the expression of SLURP2 is specifically up‐regulated by interleukin‑22 via STAT3 signaling and is completely suppressed by interferon‑γ, highlighting a cytokine‐dependent mechanism that fine‑tunes nAChR‐mediated regulation of epidermal homeostasis. (5)"}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these findings illustrate that although Lynx1 and SLURP2 share structural motifs and can both modulate nAChR function, in keratinocytes their actions are executed independently. This segregation likely preserves unique signaling roles in the regulation of cell proliferation, differentiation, and inflammatory responses in the skin as well as in other tissues.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n (1)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", (2)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", (3)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", (4)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", (5)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Fabrice Chimienti, Ronald C Hogg, Laure Plantard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of SLURP-1 as an epidermal neuromodulator explains the clinical phenotype of Mal de Meleda."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddg320"}], "href": "https://doi.org/10.1093/hmg/ddg320"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14506129"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14506129"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Inés Ibañez-Tallon, Julie M Miwa, Hai Long Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel modulation of neuronal nicotinic acetylcholine receptors by association with the endogenous prototoxin lynx1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0896-6273(02)00632-3"}], "href": "https://doi.org/10.1016/s0896-6273(02"}, {"type": "t", "text": "00632-3) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11906696"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11906696"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ekaterina N Lyukmanova, Zakhar O Shenkarev, Mikhail A Shulepko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NMR structure and action on nicotinic acetylcholine receptors of water-soluble domain of human LYNX1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.189100"}], "href": "https://doi.org/10.1074/jbc.M110.189100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21252236"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21252236"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "E N Lyukmanova, M A Shulepko, Z O Shenkarev, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Secreted Isoform of Human Lynx1 (SLURP-2): Spatial Structure and Pharmacology of Interactions with Different Types of Acetylcholine Receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep30698"}], "href": "https://doi.org/10.1038/srep30698"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27485575"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27485575"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yasuhiro Moriwaki, Kiyoko Takada, Shoutaro Tsuji, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptional regulation of SLURP2, a psoriasis-associated gene, is under control of IL-22 in the skin: A special reference to the nested gene LYNX1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int Immunopharmacol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.intimp.2015.05.030"}], "href": "https://doi.org/10.1016/j.intimp.2015.05.030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26033490"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26033490"}]}]}]}