Cptp-KO Mouse

Cptp, Ceramide-1-phosphate transfer protein, is a member of the glycolipid transfer protein (GLTP) superfamily. It shuttles ceramide-1-phosphate (C1P) between membranes, regulating cellular sphingolipid homeostasis. This function impacts programmed cell death, inflammation, autophagy, and inflammasome activation [1,3,4].

Knockdown of Cptp in human epithelial cells stimulates an 8-to 10-fold increase in autophagosomes, alters endogenous LC3-II and SQSTM1/p62 protein expression levels, and suppresses MTOR phosphorylation [3]. In THP-1 macrophage-like surveillance cells, Cptp knockdown not only induces autophagy but also elevates CASP1/caspase-1 levels and increases IL1B/interleukin-1β and IL18 release via a NLRP3-based mechanism [3]. In pancreatic cancer cells, CPTP is highly expressed, and its knockdown can inhibit cell growth and metastasis, suggesting it may function as a pro-tumorigenic gene [2].

In conclusion, Cptp is a crucial regulator of autophagy, inflammasome activation, and sphingolipid-related processes. Studies on Cptp, especially through loss-of-function models, have revealed its significance in inflammation-related diseases and cancer, providing potential therapeutic targets for these conditions.

References:

1. Gao, Yong-Guang, Zhai, Xiuhong, Boldyrev, Ivan A, Malinina, Lucy, Brown, Rhoderick E. 2021. Ceramide-1-phosphate transfer protein (CPTP) regulation by phosphoinositides. In The Journal of biological chemistry, 296, 100600. doi:10.1016/j.jbc.2021.100600. https://pubmed.ncbi.nlm.nih.gov/33781749/

2. Zhang, Yanqun, Ji, Shenying, Zhang, Xiangyu, Lam, Sin Man, Zou, Xianqiong. 2022. Human CPTP promotes growth and metastasis via sphingolipid metabolite ceramide and PI4KA/AKT signaling in pancreatic cancer cells. In International journal of biological sciences, 18, 4963-4983. doi:10.7150/ijbs.70007. https://pubmed.ncbi.nlm.nih.gov/35982909/

3. Mishra, Shrawan Kumar, Gao, Yong-Guang, Deng, Yibin, Hinchcliffe, Edward H, Brown, Rhoderick E. 2018. CPTP: A sphingolipid transfer protein that regulates autophagy and inflammasome activation. In Autophagy, 14, 862-879. doi:10.1080/15548627.2017.1393129. https://pubmed.ncbi.nlm.nih.gov/29164996/

4. Zhang, Yanqun, Zhang, Xiangyu, Lu, Mengyun, Zou, Xianqiong. 2021. Ceramide-1-phosphate and its transfer proteins in eukaryotes. In Chemistry and physics of lipids, 240, 105135. doi:10.1016/j.chemphyslip.2021.105135. https://pubmed.ncbi.nlm.nih.gov/34499882/