Clstn2, also known as calsyntenin-2, is a synaptic protein belonging to the cadherin superfamily. It plays a crucial role in learning and memory, and is involved in processes such as cell proliferation, differentiation, cell death, and tumorigenesis [1,3,4]. It may also be associated with the PI3K/AKT signaling pathway [2].

In Clstn2 knockout (KO) mice, there is a deficit of GABAergic interneurons, leading to hyperactivity, deficient spatial memory, and social behavior. Morphometric analysis shows a reduction in symmetric (inhibitory) synaptic density, length of synaptic contacts, and postsynaptic density in hippocampal and cortical neurons. Cortical neurons in KO mice have simplified synapses and altered synaptic vesicle numbers in presynaptic zones [3]. Male Clstn2-KO mice specifically exhibit deficient social motivation and recognition, indicating a gene-sex interaction on socio-emotional performance [4]. In addition, knockdown of Lnc-CLSTN2-1:1 in osteosarcoma cells significantly inhibits their proliferation, invasion, and migration, and affects the PI3K/AKT signaling pathway as well as antioxidant stress levels [2].

In conclusion, Clstn2 is essential for maintaining normal synaptic morphology and function, and is closely related to learning, memory, and social behavior in mice. Its role in the PI3K/AKT signaling pathway also has implications for cancer-related processes. The study of Clstn2 KO mouse models has provided valuable insights into its functions in these biological processes and disease-related conditions [2,3,4].

References:

1. Wijayanti, Dwi, Bai, Yangyang, Hanif, Quratulain, Guo, Zhengang, Lan, Xianyong. 2022. Goat CLSTN2 gene: tissue expression profile, genetic variation, and its associations with litter size. In Animal biotechnology, 34, 2674-2683. doi:10.1080/10495398.2022.2111311. https://pubmed.ncbi.nlm.nih.gov/35980330/

2. Lin, Hao, Wei, Xinjian, Ye, Junhong, Zeng, Yuming, Peng, Lijiao. 2024. Lnc-CLSTN2-1:1 Promotes Osteosarcoma Progression by Disrupting Redox Balance through PI3K/AKT Signaling Pathway. In Journal of Cancer, 15, 1287-1298. doi:10.7150/jca.91579. https://pubmed.ncbi.nlm.nih.gov/38356713/

3. Ranneva, Svetlana V, Maksimov, Valeriy F, Korostyshevskaja, Irina M, Lipina, Tatiana V. 2019. Lack of synaptic protein, calsyntenin-2, impairs morphology of synaptic complexes in mice. In Synapse (New York, N.Y.), 74, e22132. doi:10.1002/syn.22132. https://pubmed.ncbi.nlm.nih.gov/31529526/

4. Ranneva, S V, Pavlov, K S, Gromova, A V, Amstislavskaya, T G, Lipina, T V. 2017. Features of emotional and social behavioral phenotypes of calsyntenin2 knockout mice. In Behavioural brain research, 332, 343-354. doi:10.1016/j.bbr.2017.06.029. https://pubmed.ncbi.nlm.nih.gov/28647593/