{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nResearch on membrane‐associated modulators in the nervous system has revealed that members of the lynx family (e.g., lynx1) act as endogenous regulators of nicotinic acetylcholine receptors. These glycosylphosphatidylinositol‐anchored proteins interact directly with receptor subtypes to modulate their functional properties—enhancing receptor desensitization, altering subunit assembly, and ultimately limiting synaptic plasticity. For instance, lynx1 expression increases with age to “brake” cholinergic function in the visual cortex, restrict dendritic spine turnover, and constrain motor learning, while modifications to its expression or membrane attachment alter these processes and can even influence neurodegenerative as well as neuroprotective outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast to the well‐characterized role of lynx proteins in the brain, recent transcriptomic analyses of adipose progenitor cells have identified Small Integral Membrane Protein 10 Like 1 (SMIM10L1) as a novel regulatory molecule. Specifically, in the context of PTEN knockdown—relevant to PTEN Hamartoma Tumor Syndrome—SMIM10L1 was found to be the most significantly downregulated gene, and its loss was associated with enhanced adipocyte differentiation. The downregulation of SMIM10L1 coincided with reduced PTEN expression, elevated activity of the PI3K/AKT/mTOR cascade, and increased levels of the adipogenic transcription factor SREBP1. Computational predictions of an α‐helical structure support its membrane association, suggesting that SMIM10L1 normally acts to modulate growth signaling pathways that, when deregulated, may predispose to lipoma formation in pediatric patients."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these findings emphasize the diverse roles of membrane-associated proteins in regulating key cellular signaling networks. Whereas lynx proteins fine-tune receptor activity and neuronal plasticity to preserve circuit stability, SMIM10L1 appears to serve a pivotal function in restraining adipogenesis by modulating the PI3K/AKT/mTOR pathway. This contrast underscores the importance of context-specific regulation by membrane modulators and highlights potential therapeutic targets for disorders involving dysfunctional plasticity or aberrant tissue growth."}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "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": 2, "children": [{"type": "t", "text": "Hirofumi Morishita, Julie M Miwa, Nathaniel Heintz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lynx1, a cholinergic brake, limits plasticity in adult visual cortex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1195320"}], "href": "https://doi.org/10.1126/science.1195320"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21071629"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21071629"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Julie M Miwa, Andreas Walz "}, {"type": "b", "children": [{"type": "t", "text": "Enhancement in motor learning through genetic manipulation of the Lynx1 gene."}]}, {"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.0043302"}], "href": "https://doi.org/10.1371/journal.pone.0043302"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23139735"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23139735"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Atsuko Kobayashi, Rell L Parker, Ashley P Wright, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lynx1 supports neuronal health in the mouse dorsal striatum during aging: an ultrastructural investigation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Neurosci (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12031-014-0352-1"}], "href": "https://doi.org/10.1007/s12031-014-0352-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25027556"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25027556"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Weston A Nichols, Brandon J Henderson, Caroline Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lynx1 shifts α4β2 nicotinic receptor subunit stoichiometry by affecting assembly in the endoplasmic reticulum."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M114.573667"}], "href": "https://doi.org/10.1074/jbc.M114.573667"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25193667"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25193667"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Noreen Bukhari, Poromendro N Burman, Ayan Hussein, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Unmasking Proteolytic Activity for Adult Visual Cortex Plasticity by the Removal of Lynx1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.4315-14.2015"}], "href": "https://doi.org/10.1523/JNEUROSCI.4315-14.2015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26377459"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26377459"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Mari Sajo, Graham Ellis-Davies, Hirofumi Morishita "}, {"type": "b", "children": [{"type": "t", "text": "Lynx1 Limits Dendritic Spine Turnover in the Adult Visual Cortex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.0580-16.2016"}], "href": "https://doi.org/10.1523/JNEUROSCI.0580-16.2016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27605620"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27605620"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "M L Bychkov, A V Kirichenko, A S Paramonov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Accumulation of β-Amyloid Leads to a Decrease in Lynx1 and Lypd6B Expression in the Hippocampus and Increased Expression of Proinflammatory Cytokines in the Hippocampus and Blood Serum."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dokl Biochem Biophys (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1134/S1607672923700217"}], "href": "https://doi.org/10.1134/S1607672923700217"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37833597"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37833597"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Michèle Nebe, Stephanie Kehr, Samuel Schmitz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Small integral membrane protein 10 like 1 downregulation enhances differentiation of adipose progenitor cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2022.03.014"}], "href": "https://doi.org/10.1016/j.bbrc.2022.03.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35290761"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35290761"}]}]}]}