{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlthough SPATA31D3 is less well characterized than classical actin‐regulatory kinases, accumulating evidence from studies on cytoskeletal reorganization indicates that factors governing actin assembly—including the Rho/ROCK–LIMK–cofilin cascade—are central to many cellular processes. In paradigms where transforming growth factor beta (TGF‑β) signaling and small GTPases trigger rapid actin polymerization and stress fiber formation, LIM kinases phosphorylate cofilin to mediate cytoskeletal remodeling, thereby affecting cell adhesion, motility, and morphology. By analogy, SPATA31D3 may participate in or modulate these pathways, contributing to the regulation of actin dynamics in response to extracellular signals."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStudies in diverse model systems have established that the reorganization of the actin cytoskeleton governs important biological events ranging from epithelial migration and synaptic function to embryonic development and mechanosensitive osteoblast differentiation. The coordinated activity of RhoA, ROCK, and LIMK is critical for processes such as eyelid closure, oocyte spindle migration, and proper synaptic transmission, while altered cytoskeletal dynamics also impact cell proliferation and differentiation in pathological settings like cancer progression and tissue fibrosis. These multifaceted roles of actin regulators suggest that SPATA31D3 might similarly be involved—either as an upstream modulator or as part of a broader network influencing cytoskeletal architecture—to fine‐tune cellular responses during development and stress."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging research further implicates actin-regulatory signaling in neural plasticity, platelet functionality, and fibrotic remodeling after injury. Investigations into synaptic scaling, cortical development, and tumor metastasis reveal that modulating cofilin activity via LIM kinases can have profound effects on cell structure and function. Although direct experimental data on SPATA31D3 remain limited, its inclusion in studies addressing the broader spectrum of actin dynamics raises the possibility that it contributes to these critical processes. Clarifying SPATA31D3’s role—whether by interfacing with key signaling molecules like LIMK or affecting downstream events such as receptor internalization and transcriptional regulation—could provide valuable insights into mechanisms underlying cell motility, differentiation, and pathological remodeling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yanghong Meng, Hisaaki Takahashi, Jinsong Meng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of ADF/cofilin phosphorylation and synaptic function by LIM-kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropharmacology (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuropharm.2004.06.030"}], "href": "https://doi.org/10.1016/j.neuropharm.2004.06.030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15458846"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15458846"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lina Vardouli, Aristidis Moustakas, Christos Stournaras "}, {"type": "b", "children": [{"type": "t", "text": "LIM-kinase 2 and cofilin phosphorylation mediate actin cytoskeleton reorganization induced by transforming growth factor-beta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M402651200"}], "href": "https://doi.org/10.1074/jbc.M402651200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15647284"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15647284"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Seiichi Koike, Kazuko Keino-Masu, Tatsuyuki Ohto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Autotaxin/lysophospholipase D-mediated lysophosphatidic acid signaling is required to form distinctive large lysosomes in the visceral endoderm cells of the mouse yolk sac."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.012716"}], "href": "https://doi.org/10.1074/jbc.M109.012716"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19808661"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19808661"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yi-ping Zhang, Feng Qin, Chang-jing Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Effects of LIMK2 RNA interference on the mechanosensitivity of c-fos gene in osteoblast]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Zhonghua Yi Xue Za Zhi (2009)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20193279"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20193279"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Dennis S Rice, Gwenn M Hansen, Feng Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Keratinocyte migration in the developing eyelid requires LIMK2."}]}, {"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.0047168"}], "href": "https://doi.org/10.1371/journal.pone.0047168"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23071748"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23071748"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Filipe C Lourenço, June Munro, Jennifer Brown, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reduced LIMK2 expression in colorectal cancer reflects its role in limiting stem cell proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gut (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/gutjnl-2012-303883"}], "href": "https://doi.org/10.1136/gutjnl-2012-303883"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23585469"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23585469"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Zhi Yang, Shuyi Tan, Yun Shen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of FSS-induced actin cytoskeleton reorganization by silencing LIMK2 gene increases the mechanosensitivity of primary osteoblasts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bone (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bone.2014.12.024"}], "href": "https://doi.org/10.1016/j.bone.2014.12.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25549868"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25549868"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Xiangyu Yang, Guiqin He, Xiaoyun Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transient inhibition of LIMKs significantly attenuated central sensitization and delayed the development of chronic pain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropharmacology (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuropharm.2017.06.031"}], "href": "https://doi.org/10.1016/j.neuropharm.2017.06.031"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28669900"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28669900"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Xing Duan, Yu Zhang, Kun-Lin Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The small GTPase RhoA regulates the LIMK1/2-cofilin pathway to modulate cytoskeletal dynamics in oocyte meiosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.26450"}], "href": "https://doi.org/10.1002/jcp.26450"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29319181"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29319181"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Xing Duan, Hao-Lin Zhang, Lan-Lan Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of LIMK1/2 in actin assembly during mouse embryo development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15384101.2018.1482138"}], "href": "https://doi.org/10.1080/15384101.2018.1482138"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29943641"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29943641"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Qiaojun Fang, Yuhua Zhang, Peng Da, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deletion of Limk1 and Limk2 in mice does not alter cochlear development or auditory function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-019-39769-z"}], "href": "https://doi.org/10.1038/s41598-019-39769-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30833597"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30833597"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Rui Mao, Rui Deng, Yan Wei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LIMK1 and LIMK2 regulate cortical development through affecting neural progenitor cell proliferation and migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Brain (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13041-019-0487-7"}], "href": "https://doi.org/10.1186/s13041-019-0487-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31319858"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31319858"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Juliana Antonipillai, Kevin Mittelstaedt, Sheena Rigby, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LIM kinase 2 (LIMK2) may play an essential role in platelet function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2020.111822"}], "href": "https://doi.org/10.1016/j.yexcr.2020.111822"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31926945"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31926945"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Y-L Huang, X-H Li, H Ma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Metabolites of intestinal microflora upregulate miR-192-5p to suppress proliferation of colon cancer cells via RhoA-ROCK-LIMK2 pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Rev Med Pharmacol Sci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.26355/eurrev_202002_20357"}], "href": "https://doi.org/10.26355/eurrev_202002_20357"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32141548"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32141548"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Qun Huang, Hao Chai, Shendong Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "0.5‑Gy X‑ray irradiation induces reorganization of cytoskeleton and differentiation of osteoblasts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2021.12018"}], "href": "https://doi.org/10.3892/mmr.2021.12018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33760136"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33760136"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Zikai Zhou, Guiqin He, Xiaoyun Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NGPF2 triggers synaptic scaling up through ALK-LIMK-cofilin-mediated mechanisms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2021.109515"}], "href": "https://doi.org/10.1016/j.celrep.2021.109515"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34407403"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34407403"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Parmanand Malvi, Dhana Sekhar Reddy, Raj Kumar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LIMK2 promotes melanoma tumor growth and metastasis through G3BP1-ESM1 pathway-mediated apoptosis inhibition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-023-02658-x"}], "href": "https://doi.org/10.1038/s41388-023-02658-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36922679"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36922679"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Chenyi Gong, Lei Chang, Rong Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LIM kinase 2 activates cardiac fibroblasts and exacerbates postinfarction left ventricular remodeling via crosstalk between the canonical and non-canonical Wnt pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pharmacol Res (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.phrs.2024.107347"}], "href": "https://doi.org/10.1016/j.phrs.2024.107347"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39153710"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39153710"}]}]}]}