Septin8, a member of the septin protein family, is involved in diverse physiological functions. Septins play a role in the formation of specialized cytoskeletal structures, and Septin8 is implicated in processes such as spine morphogenesis and dendritic branching through palmitoylation [3]. It may also be associated with the sorting and accumulation of β -secretase, and is part of a scaffolding septin filament in the central nervous system myelin formation [4,5].

Genetic deletion of Sept8 in mice led to deficits in learning and memory and promoted anxiety-like behaviors, suggesting its role in neuronal morphology and function related to cognition [3]. In chronic kidney disease (CKD) research, a missense variant within Sept8 was identified as a candidate for urinary protein excretion in rats. Sept8/SEPTIN8 expression increased in rats with elevated urinary protein excretion and tubulointerstitial injury, as well as in an in vitro hypoxia model of human tubule, indicating its role in cellular organization and structure in response to environmental stress [1]. In prostate cancer, double knockout of SEPTIN8 along with NUDT5 significantly suppressed the proliferation, invasion, and migration of prostate cancer cells, suggesting potential new treatment approaches [2].

In conclusion, Septin8 is essential for various biological processes, including neuronal function, cellular organization under stress, and in cancer cell behavior. The gene knockout studies in mice and the use of a rat genetic model in CKD research have provided valuable insights into Septin8's role in these processes and associated disease conditions, highlighting its potential as a therapeutic target in related diseases.

References:

1. Keele, Gregory R, Prokop, Jeremy W, He, Hong, Garrett, Michael R, Solberg Woods, Leah C. 2021. Sept8/SEPTIN8 involvement in cellular structure and kidney damage is identified by genetic mapping and a novel human tubule hypoxic model. In Scientific reports, 11, 2071. doi:10.1038/s41598-021-81550-8. https://pubmed.ncbi.nlm.nih.gov/33483609/

2. Sun, Rui, A, Jun, Yu, Haolan, Gao, Xu, Yang, Chenghua. . Proteomic landscape profiling of primary prostate cancer reveals a 16-protein panel for prognosis prediction. In Cell reports. Medicine, 5, 101679. doi:10.1016/j.xcrm.2024.101679. https://pubmed.ncbi.nlm.nih.gov/39168102/

3. Liu, Huicong, Yan, Peipei, Wu, Can, Lu, Kefeng, Kong, Eryan. 2023. Palmitoylated Sept8-204 modulates learning and anxiety by regulating filopodia arborization and actin dynamics. In Science signaling, 16, eadi8645. doi:10.1126/scisignal.adi8645. https://pubmed.ncbi.nlm.nih.gov/38051778/

4. Marttinen, Mikael, Ferreira, Catarina B, Paldanius, Kaisa M A, Haapasalo, Annakaisa, Hiltunen, Mikko. 2020. Presynaptic Vesicle Protein SEPTIN5 Regulates the Degradation of APP C-Terminal Fragments and the Levels of Aβ. In Cells, 9, . doi:10.3390/cells9112482. https://pubmed.ncbi.nlm.nih.gov/33203136/

5. Martens, Ann-Kristin, Erwig, Michelle, Patzig, Julia, Füchtbauer, Ernst-Martin, Werner, Hauke B. 2022. Targeted inactivation of the Septin2 and Septin9 genes in myelinating Schwann cells of mice. In Cytoskeleton (Hoboken, N.J.), 80, 290-302. doi:10.1002/cm.21736. https://pubmed.ncbi.nlm.nih.gov/36378242/