{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSEPTIN8 is a member of the evolutionarily conserved septin family of cytosolic GTP‐binding proteins that assemble into higher order complexes. Initial studies demonstrated that SEPTIN8, like other septins, contains unique N- and C-terminal regions flanking a conserved central GTPase core, which governs both homotypic and heterotypic interactions with fellow septins. In human platelets and neurons, SEPTIN8 interacts directly with other septins such as SEPT5 and SEPT4, with proper subcellular localization to vesicle‐like structures dependent on the co‐expression of these partners. This assembly underlies its role in facilitating membrane remodeling events including exocytosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn neuronal cells, SEPTIN8 has emerged as a key regulator of protein trafficking that impacts neurodegenerative processes. A specific SEPTIN8 transcript variant modulates β‐amyloidogenic processing by influencing the intracellular sorting and stability of BACE1, the enzyme responsible for the cleavage of amyloid precursor protein (APP). This mechanism appears to affect soluble APPβ and Aβ levels, thereby linking SEPTIN8 to Alzheimer’s disease pathology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond the nervous system, SEPTIN8 fulfills important roles in cellular stress responses. In a rat model of chronic kidney disease, a missense variant in Sept8 was implicated in altered urinary protein excretion and tubulointerstitial injury. Here, SEPTIN8 expression was upregulated under hypoxic conditions, concomitant with its redistribution from organized microtubule-associated structures to actin-rich regions, suggestive of a role in maintaining cytoskeletal integrity during environmental stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the brain, a specific SEPTIN8 isoform (Sept8-204) is predominantly expressed in neurons where its function is tightly regulated by palmitoylation. Palmitoylated Sept8-204 associates with filamentous actin to promote cytoskeletal dynamics that drive filopodia formation and neurite arborization, which are essential for proper spine morphology and cognitive function. Loss or mutation of key cysteine residues abrogates these effects, underscoring the importance of post-translational modification in SEPTIN8’s function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSEPTIN8 is also expressed in ocular tissues, particularly within proliferative retinal membranes associated with conditions such as proliferative vitreoretinopathy and diabetic retinopathy. Its prominent localization around alpha-granules in these membranes suggests that SEPTIN8 contributes to the cytoskeletal framework underlying membrane development and remodeling in the retina."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBiochemical analyses of recombinant SEPTIN8 constructs have further revealed that its conserved central domain, together with flanking terminal regions, is critical for proper folding and the formation of dimeric—and possibly higher order—oligomers. Such structural properties are likely to be fundamental for its interactions within septin complexes and for executing its cellular functions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Constantino Martínez, Miguel A Sanjuan, Judith A Dent, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human septin-septin interactions as a prerequisite for targeting septin complexes in the cytosol."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20040372"}], "href": "https://doi.org/10.1042/BJ20040372"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15214843"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15214843"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Susanne Bläser, Julia Horn, Paul Würmell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The novel human platelet septin SEPT8 is an interaction partner of SEPT4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Haemost (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1160/TH03-09-0578"}], "href": "https://doi.org/10.1160/TH03-09-0578"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15116257"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15116257"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kaisa M A Kurkinen, Mikael Marttinen, Laura Turner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SEPT8 modulates β-amyloidogenic processing of APP by affecting the sorting and accumulation of BACE1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.185215"}], "href": "https://doi.org/10.1242/jcs.185215"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27084579"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27084579"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Gregory R Keele, Jeremy W Prokop, Hong He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sept8/SEPTIN8 involvement in cellular structure and kidney damage is identified by genetic mapping and a novel human tubule hypoxic model."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-021-81550-8"}], "href": "https://doi.org/10.1038/s41598-021-81550-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33483609"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33483609"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Huicong Liu, Peipei Yan, Can Wu, et al. 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