{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nIgSF9b is a brain‐specific, homophilic adhesion molecule prominently expressed in GABAergic interneurons, where it preferentially localizes at inhibitory synapses. It plays a crucial role in the development and organization of inhibitory synapses by forming a distinct subsynaptic domain separate from the gephyrin- and GABAA receptor–rich domains. IgSF9b interacts with neuroligin-2 via the multi-PDZ protein S-SCAM, suggesting that the proper clustering of these proteins is essential for synaptic integrity and efficient inhibitory transmission. (‑"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "‑)\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its synaptic organizing function, IgSF9b is implicated in the regulation of anxiety-related neural circuits in the amygdala. In mouse models deficient for neuroligin-2, deletion of IgSF9b was found to normalize anxiety-like behaviors by exerting differential effects at inhibitory synapses within the centromedial amygdala. These findings position IgSF9b as a key modulator of inhibitory signaling in emotion-relevant circuits and highlight its potential as a target for anxiolytic therapies. (‑"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "‑)\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, proteomic analyses have revealed that IgSF9b interacts with Prickle2, an interaction that is critical for maintaining the cytoarchitecture of the axon initial segment (AIS). Knockdown studies showed that loss of proper IgSF9b localization disrupts the distribution of ankyrin-G and voltage-gated sodium channels at the AIS, leading to changes in neuronal excitability and network dynamics. Such alterations may contribute to the pathophysiology observed in neurodevelopmental disorders like autism spectrum disorder and epilepsy, thereby linking IgSF9b to broader neuropsychiatric vulnerabilities. (‑"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "‑)\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jooyeon Woo, Seok-Kyu Kwon, Jungyong Nam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The adhesion protein IgSF9b is coupled to neuroligin 2 via S-SCAM to promote inhibitory synapse development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201209132"}], "href": "https://doi.org/10.1083/jcb.201209132"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23751499"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23751499"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Olga Babaev, Hugo Cruces-Solis, Carolina Piletti Chatain, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IgSF9b regulates anxiety behaviors through effects on centromedial amygdala inhibitory synapses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-018-07762-1"}], "href": "https://doi.org/10.1038/s41467-018-07762-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30573727"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30573727"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Md Imrul Hasan Chowdhury, Tomoki Nishioka, Noriko Mishima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prickle2 and Igsf9b Coordinately Regulate the Cytoarchitecture of the Axon Initial Segment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Struct Funct (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1247/csf.20028"}], "href": "https://doi.org/10.1247/csf.20028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32641624"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32641624"}]}]}]}