{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe septin protein family plays a pivotal role in orchestrating membrane organization and vesicle trafficking, with particular emphasis on CDCrel‐1/SEPTIN5. In platelets, for example, CDCrel‐1 is a substrate for protein kinases activated by agonists and is integrated into macromolecular complexes that include key factors necessary for granule secretion, thereby modulating exocytosis and membrane remodeling required for proper platelet function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn neural tissues, septin proteins—especially SEPTIN5—serve as dynamic regulators at presynaptic terminals. They help control the spatial coupling of Ca²⁺ channels to synaptic vesicles, thereby influencing neurotransmitter release, synaptic vesicle pool maintenance, and overall synaptic integrity. Genetic manipulations of SEPTIN5 have revealed its involvement in affective behaviors, cognitive processes, and motor function, with its deficiency or altered phosphorylation status being linked to neuropsychiatric conditions, Parkinson’s disease models, and modifications in synaptic plasticity. Moreover, differential expression and isoform‐specific post‐translational modifications underscore the complexity of septin functions in vesicle docking, exocytosis, and autoimmunity in neuronal compartments."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAlthough none of the provided abstracts directly mention ANKRD40CL, the collective findings on septin biology are informative for understanding similar regulatory mechanisms in related proteins. In disease contexts, septin dysregulation via altered expression levels or post‐translational modifications (such as phosphorylation at specific residues) is associated with neurodegenerative pathologies, including Alzheimer’s disease, as well as neoplastic processes in cancer where septin levels correlate with immune cell infiltration and tumor progression. Complementary studies also extend the functional landscape of septins to include the regulation of vesicle structure (as seen in the interplay between SEPTIN5 and other vesicle‐associated septins) and underline the importance of lipid modifications (e.g., palmitoylation) in maintaining synaptic vesicle dynamics. In addition, while some studies have explored alternative pathways in cancers like cervical and breast cancer, the central theme remains that precise control of membrane trafficking and compartmentalization—functions shared by the septin family—may also be relevant to understanding the cellular role of ANKRD40CL."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Judith Dent, Kazunobu Kato, Xiao-Rong Peng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A prototypic platelet septin and its participation in secretion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.052715199"}], "href": "https://doi.org/10.1073/pnas.052715199"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11880646"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11880646"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yi-Mei Yang, Michael J Fedchyshyn, Giovanbattista Grande, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Septins regulate developmental switching from microdomain to nanodomain coupling of Ca(2+) influx to neurotransmitter release at a central synapse."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2010.06.003"}], "href": "https://doi.org/10.1016/j.neuron.2010.06.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20624595"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20624595"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Go Suzuki, Kathryn M Harper, Takeshi Hiramoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sept5 deficiency exerts pleiotropic influence on affective behaviors and cognitive functions in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddp086"}], "href": "https://doi.org/10.1093/hmg/ddp086"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19240081"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19240081"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jin H Son, Hibiki Kawamata, Myung S Yoo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neurotoxicity and behavioral deficits associated with Septin 5 accumulation in dopaminergic neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurochem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1471-4159.2005.03257.x"}], "href": "https://doi.org/10.1111/j.1471-4159.2005.03257.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16092945"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16092945"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Kathryn M Harper, Takeshi Hiramoto, Kenji Tanigaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Alterations of social interaction through genetic and environmental manipulation of the 22q11.2 gene Sept5 in the mouse brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/dds180"}], "href": "https://doi.org/10.1093/hmg/dds180"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22589251"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22589251"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Christopher W Tsang, Michael Fedchyshyn, John Harrison, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Superfluous role of mammalian septins 3 and 5 in neuronal development and synaptic transmission."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00035-08"}], "href": "https://doi.org/10.1128/MCB.00035-08"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18809578"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18809578"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Makoto Taniguchi, Masato Taoka, Makoto Itakura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphorylation of adult type Sept5 (CDCrel-1) by cyclin-dependent kinase 5 inhibits interaction with syntaxin-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M609457200"}], "href": "https://doi.org/10.1074/jbc.M609457200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17224448"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17224448"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Shannon R Hinson, Josephe A Honorat, Ethan M Grund, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Septin-5 and -7-IgGs: Neurologic, Serologic, and Pathophysiologic Characteristics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Neurol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ana.26482"}], "href": "https://doi.org/10.1002/ana.26482"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36053822"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36053822"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Akiko Asada, Junya Takahashi, Makoto Taniguchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neuronal expression of two isoforms of mouse Septin 5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jnr.22294"}], "href": "https://doi.org/10.1002/jnr.22294"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19937814"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19937814"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Ming Chang, Yu He, Cong Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of SEPTIN5 inhibits prostate cancer progression by increasing CD8"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " T cell infiltration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biol Sci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/ijbs.76573"}], "href": "https://doi.org/10.7150/ijbs.76573"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36439885"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36439885"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Mikael Marttinen, Catarina B Ferreira, Kaisa M A Paldanius, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Presynaptic Vesicle Protein SEPTIN5 Regulates the Degradation of APP C-Terminal Fragments and the Levels of Aβ."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cells (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/cells9112482"}], "href": "https://doi.org/10.3390/cells9112482"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33203136"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33203136"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Atsuhiro Yoshida, Norio Yamamoto, Makoto Kinoshita, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Localization of septin proteins in the mouse cochlea."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hear Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.heares.2012.04.015"}], "href": "https://doi.org/10.1016/j.heares.2012.04.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22575789"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22575789"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Catarina B Ferreira, Mikael Marttinen, Joana E Coelho, et al. "}, {"type": "b", "children": [{"type": "t", "text": "S327 phosphorylation of the presynaptic protein SEPTIN5 increases in the early stages of neurofibrillary pathology and alters the functionality of SEPTIN5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurobiol Dis (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.nbd.2021.105603"}], "href": "https://doi.org/10.1016/j.nbd.2021.105603"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34954322"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34954322"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Pin Hu, Guiju Zhou, Xiaohui Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA Linc00483 accelerated tumorigenesis of cervical cancer by regulating miR-508-3p/RGS17 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Life Sci (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.lfs.2019.116789"}], "href": "https://doi.org/10.1016/j.lfs.2019.116789"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31454494"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31454494"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Y-S Qiao, J-H Zhou, B-H Jin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LINC00483 is regulated by IGF2BP1 and participates in the progression of breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Rev Med Pharmacol Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.26355/eurrev_202102_24846"}], "href": "https://doi.org/10.26355/eurrev_202102_24846"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33629308"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33629308"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Huicong Liu, Rong Tan, Jia Tong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Palmitoylation is required for Sept8-204 and Sept5 to form vesicle-like structure and colocalize with synaptophysin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.30529"}], "href": "https://doi.org/10.1002/jcb.30529"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38308620"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38308620"}]}]}]}