Syt13, an atypical member of the vesicle trafficking synaptotagmin protein family, is a Ca2+-independent protein. It plays diverse roles in various biological processes. It is involved in the secretion of neurotransmitters by synaptic vesicles, and has functions in cell migration, proliferation, and cell cycle regulation. It is also associated with multiple signaling pathways, such as the FAK/AKT signaling pathway [2,5]. Syt13 is highly expressed in the endocrine lineages of major organs like the brain, intestine, and pancreas, serving as a neuroendocrine marker [8].

In disease-related research, in lung adenocarcinoma cell lines A549 and H1299, knockdown of Syt13 led to decreased proliferation, clonality, cell cycle arrest, and enhanced apoptosis. In H1299 cells, there was also a decreased migration ability [1]. In breast cancer, knockdown of Syt13 in MCF-7 cells inhibited cell proliferation, induced cell cycle arrest in G1 phase, repressed migration and invasion, and induced apoptosis. Overexpression in MDA-MB-231 cells had opposite effects. The mechanism was related to the activation of the FAK/AKT signaling pathway [2]. In gastric cancer, SYT13 mRNA levels in peritoneal lavage fluid were significantly associated with shorter peritoneal recurrence-free survival and overall survival, and could be a predictor of peritoneal recurrence [3]. In motor neuron diseases like ALS and SMA, overexpression of SYT13 in patient motor neurons in vitro improved their survival and increased axon lengths. Gene therapy with Syt13 prolonged the lifespan of ALS and SMA mice by preserving motor neurons and delaying muscle denervation [4]. In pancreatic development, knockout of Syt13 in mice impaired endocrine cell egression and skewed the α-to-β-cell ratio [6]. In insulin-secreting cells, downregulation of Syt13 decreased insulin secretion induced by glucose and K+ [7].

In conclusion, Syt13 is crucial for normal biological functions such as neuroendocrine cell activity, pancreatic islet formation, and insulin secretion. In disease conditions, it is involved in the development of various cancers and motor neuron diseases. The use of gene knockdown or knockout models in cell lines and animal models has significantly contributed to understanding its role in these biological processes and diseases, providing potential targets for disease treatment.

References:

1. Zhang, Liyan, Fan, Bijun, Zheng, Yu, Zhang, Tiancheng, Tan, Xiaoming. 2019. Identification SYT13 as a novel biomarker in lung adenocarcinoma. In Journal of cellular biochemistry, 121, 963-973. doi:10.1002/jcb.29224. https://pubmed.ncbi.nlm.nih.gov/31625195/

2. Zhang, Yi-Dan, Zhong, Rui, Liu, Jin-Quan, Wang, Teng, Liu, Jin-Tao. 2023. Role of synaptotagmin 13 (SYT13) in promoting breast cancer and signaling pathways. In Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 25, 1629-1640. doi:10.1007/s12094-022-03058-5. https://pubmed.ncbi.nlm.nih.gov/36630025/

3. Nakanishi, Koki, Kanda, Mitsuro, Umeda, Shinichi, Yamada, Suguru, Kodera, Yasuhiro. 2019. The levels of SYT13 and CEA mRNAs in peritoneal lavages predict the peritoneal recurrence of gastric cancer. In Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 22, 1143-1152. doi:10.1007/s10120-019-00967-3. https://pubmed.ncbi.nlm.nih.gov/31055693/

4. Nizzardo, M, Taiana, M, Rizzo, F, Hedlund, E, Corti, S. 2020. Synaptotagmin 13 is neuroprotective across motor neuron diseases. In Acta neuropathologica, 139, 837-853. doi:10.1007/s00401-020-02133-x. https://pubmed.ncbi.nlm.nih.gov/32065260/

5. Kanda, Mitsuro, Kasahara, Yuuya, Shimizu, Dai, Kodera, Yasuhiro, Obika, Satoshi. 2020. Amido-Bridged Nucleic Acid-Modified Antisense Oligonucleotides Targeting SYT13 to Treat Peritoneal Metastasis of Gastric Cancer. In Molecular therapy. Nucleic acids, 22, 791-802. doi:10.1016/j.omtn.2020.10.001. https://pubmed.ncbi.nlm.nih.gov/33230476/

6. Bakhti, Mostafa, Bastidas-Ponce, Aimée, Tritschler, Sophie, Coskun, Ünal, Lickert, Heiko. 2022. Synaptotagmin-13 orchestrates pancreatic endocrine cell egression and islet morphogenesis. In Nature communications, 13, 4540. doi:10.1038/s41467-022-31862-8. https://pubmed.ncbi.nlm.nih.gov/35927244/

7. Ofori, Jones K, Karagiannopoulos, Alexandros, Barghouth, Mohammad, Wendt, Anna, Eliasson, Lena. 2022. The highly expressed calcium-insensitive synaptotagmin-11 and synaptotagmin-13 modulate insulin secretion. In Acta physiologica (Oxford, England), 236, e13857. doi:10.1111/apha.13857. https://pubmed.ncbi.nlm.nih.gov/35753051/

8. Tarquis-Medina, Marta, Scheibner, Katharina, González-García, Ismael, Lickert, Heiko, Bakhti, Mostafa. 2021. Synaptotagmin-13 Is a Neuroendocrine Marker in Brain, Intestine and Pancreas. In International journal of molecular sciences, 22, . doi:10.3390/ijms222212526. https://pubmed.ncbi.nlm.nih.gov/34830411/