{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNCKIPSD, also known as SPIN90, is a multifunctional adaptor protein that orchestrates the dynamic regulation of the actin cytoskeleton. Acting as a binding partner for Nck, betaPIX, WASP, and IRSp53, SPIN90 bridges signaling pathways to promote actin polymerization through its direct activation of the Arp2/3 complex and interaction with formin proteins. Through its proline‐rich and SH3 domains, it facilitates the formation of lamellipodia and membrane ruffles by coupling external signals such as PDGF and Src kinase activity to local actin nucleation and polymerization, thereby playing a key role in cell shape changes and motility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in cytoskeletal remodeling, SPIN90 contributes to membrane trafficking and cell motility by regulating endocytosis. It is essential for proper vesicle formation and the intracellular trafficking of receptors such as the epidermal growth factor receptor (EGFR), thereby modulating receptor turnover and downstream proliferative signaling. Phosphorylation events enable SPIN90 to act as an adaptor linking inactive Rab5 and its guanine nucleotide exchange factor Gapex5, fostering Rab5 activation and efficient endosomal transport. In parallel, loss of SPIN90 triggers increased microtubule acetylation, which in turn influences nuclear localization of mechanotransducers like YAP, impacting cancer-associated fibroblast activation and tumor progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn neurons, SPIN90 is a crucial mediator of synaptic structure and plasticity. Its recruitment to dendritic spines—governed by tyrosine phosphorylation from Src kinase—enables SPIN90 to interact with key postsynaptic scaffold proteins such as PSD95 and Shank. This targeting not only bolsters synaptic activity and spine head enlargement but also regulates actin turnover by modulating cofilin activity through phosphorylation/dephosphorylation cycles. Such mechanisms contribute to the dynamic remodeling of dendritic spines necessary for synaptic plasticity and efficient signal transduction at the postsynaptic density."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Chol Seung Lim, Sung Hyun Kim, Jin Gyoung Jung, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Interaction of SPIN90 with the Arp2/3 complex mediates lamellipodia and actin comet tail formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M504450200"}], "href": "https://doi.org/10.1074/jbc.M504450200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16253999"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16253999"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Mikko Rönty, Anu Taivainen, Leena Heiska, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Palladin interacts with SH3 domains of SPIN90 and Src and is required for Src-induced cytoskeletal remodeling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2007.04.030"}], "href": "https://doi.org/10.1016/j.yexcr.2007.04.030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17537434"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17537434"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Carmen Teodorof, Jeom Il Bae, Seon-Myung Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPIN90-IRSp53 complex participates in Rac-induced membrane ruffling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2009.05.010"}], "href": "https://doi.org/10.1016/j.yexcr.2009.05.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19460367"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19460367"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Qing Luan, Su-Ling Liu, Luke A Helgeson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure of the nucleation-promoting factor SPIN90 bound to the actin filament nucleator Arp2/3 complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embj.2018100005"}], "href": "https://doi.org/10.15252/embj.2018100005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30322896"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30322896"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Hyejin Oh, Hwan Kim, Kyung-Hwun Chung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPIN90 knockdown attenuates the formation and movement of endosomal vesicles in the early stages of epidermal growth factor receptor endocytosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0082610"}], "href": "https://doi.org/10.1371/journal.pone.0082610"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24340049"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24340049"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Eunae You, Yun Hyun Huh, Ahreum Kwon, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "SPIN90 dephosphorylation is required for cofilin-mediated actin depolymerization in NMDA-stimulated hippocampal neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Life Sci (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00018-013-1391-4"}], "href": "https://doi.org/10.1007/s00018-013-1391-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23765104"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23765104"}]}]}]}