{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSpire1 is a versatile actin nucleator that functions as a molecular hub for organizing filament assembly during key developmental events. It cooperates with formins and profilin to promote rapid, processive actin filament formation needed for oocyte polarity and asymmetric cell division. Structural studies have revealed that conserved interactions—mediated by Spire1’s kinase‐non catalytic (KIND) domain with the C‐terminal motifs of formins such as Formin-2—drive a “ping-pong” mechanism at filament barbed ends, where Spire1 alternately recruits and then is displaced by formins to regulate dynamic actin meshworks. This coordinated activity is central to oocyte maturation and spindle translocation, underscoring its essential role in developmental polarity and cell division."}, {"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": "\nIn addition to its cytoplasmic roles in development, specialized Spire1 isoforms are dedicated to regulating organellar actin dynamics. A mitochondrial-targeted variant, Spire1C, localizes to sites where endoplasmic reticulum tubules cradle mitochondria, and in cooperation with the formin INF2, nucleates actin to generate constriction forces that drive mitochondrial division. In the nucleus, Spire1 (in concert with its paralogue Spire2) is implicated in assembling filamentous actin in response to stress and DNA damage—an activity that facilitates efficient double-strand break clearance and safeguards genome integrity. Moreover, phosphorylation events mediated by kinases such as DYRK1A fine-tune Spire1’s recruitment to damaged chromatin, thereby modulating nuclear actin polymerization during early DNA repair responses."}, {"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": "\nSpire1 further influences diverse cellular processes that extend to cell invasion, vesicular trafficking, and specialized exocytic events. At invadosomes, Spire1 is recruited into multiprotein complexes with formin mDia1 and Rab3A to coordinate actin dynamics that underlie extracellular matrix degradation and metastatic potential. During pathogenic infections, distinct SPIRE isoforms modulate host-pathogen interactions by differentially affecting bacterial binding and intracellular replication. In endothelial cells, Spire1 partners with Myosin Vc to drive the formation of actin rings that facilitate the fusion of Weibel–Palade bodies and the regulated release of von Willebrand factor. Finally, Spire1 expression itself can be tightly regulated at the translational level by long non-coding RNAs, as exemplified by the lnc-SMaRT-mediated repression during skeletal muscle differentiation. Together, these multifaceted roles highlight Spire1 as a critical regulator of actin-dependent cellular dynamics across a spectrum of physiological contexts."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Montserrat Bosch, Kim Ho Diep Le, Beata Bugyi, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Spire and Formin 2 synergize and antagonize in regulating actin assembly in meiosis by a ping-pong mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pbio.1001795"}], "href": "https://doi.org/10.1371/journal.pbio.1001795"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24586110"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24586110"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Pierre Montaville, Sonja Kühn, Christel Compper, et al. 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