LCP1, also known as Lymphocyte cytosolic protein 1, is an actin-binding protein that facilitates cell migration, immune responses, actin polymerization, cytoskeletal rearrangements, and phagocytosis [1,2,5,6]. It is involved in multiple signaling pathways, such as the mTORC2/AKT, JAK2/STAT3, and ROS-ATM-ERK1/2 pathways [4,5,6]. LCP1 is of great biological importance as it impacts various cellular functions and is associated with multiple diseases [1-10]. Genetic models, like knockout mouse models, have been crucial in studying its functions.

In ischemic stroke, knockdown of LCP1 in monocyte-derived macrophages (MoDMs) protected against ischemic infarction, improved neurological behaviors, reduced neuroinflammation, and attenuated lymphopenia. It also altered immune cell signaling and metabolism, with Lcp1high monocytes/macrophages showing enrichment in fatty acid and glycolysis metabolism [1]. In a mouse osteoarthritis (OA) model, Lcp1 knockout mice had decreased subchondral bone remodeling and retarded cartilage degeneration, as Lcp1 knockout impeded angiogenesis and maintained a hypoxic environment in joints [3]. In hypereosinophilia, enzastaurin, a PKCβ selective inhibitor, dephosphorylated and inactivated LCP1 in FIP1L1-PDGFRA-positive Eol-1 cells, reducing cell proliferation, metabolic activity, and colony formation, and enhancing apoptosis and impairing migration [5].

In conclusion, LCP1 plays essential roles in cell migration, immune responses, and metabolism. Gene knockout models, especially in mouse models, have revealed its significant contributions in disease areas such as ischemic stroke, osteoarthritis, and hypereosinophilia, providing valuable insights for potential therapeutic strategies targeting LCP1 in these diseases [1,3,5].

References:

1. Wang, Yan, Yin, Qianqian, Yang, Decao, Chen, Xiaoyuan, Zhao, Heng. 2024. LCP1 knockdown in monocyte-derived macrophages: mitigating ischemic brain injury and shaping immune cell signaling and metabolism. In Theranostics, 14, 159-175. doi:10.7150/thno.88678. https://pubmed.ncbi.nlm.nih.gov/38164159/

2. Zhang, Wei, Xu, Liang, Yu, Zhenfei, Liu, Jingquan, Zhou, Jianming. 2022. Inhibition of the Glycolysis Prevents the Cerebral Infarction Progression Through Decreasing the Lactylation Levels of LCP1. In Molecular biotechnology, 65, 1336-1345. doi:10.1007/s12033-022-00643-5. https://pubmed.ncbi.nlm.nih.gov/36574182/

3. Zhang, Hao, Wang, Lipeng, Cui, Jin, Chen, Xiao, Su, Jiacan. 2023. Maintaining hypoxia environment of subchondral bone alleviates osteoarthritis progression. In Science advances, 9, eabo7868. doi:10.1126/sciadv.abo7868. https://pubmed.ncbi.nlm.nih.gov/37018403/

4. Gai, Minxue, Zhao, Lanlan, Li, Hongqi, Wang, Fei, Liu, Ming. 2024. LCP1 promotes ovarian cancer cell resistance to olaparib by activating the JAK2/STAT3 signalling pathway. In Cancer biology & therapy, 25, 2432117. doi:10.1080/15384047.2024.2432117. https://pubmed.ncbi.nlm.nih.gov/39588922/

5. Ma, Guangxin, Gezer, Deniz, Herrmann, Oliver, Koschmieder, Steffen, Chatain, Nicolas. 2019. LCP1 triggers mTORC2/AKT activity and is pharmacologically targeted by enzastaurin in hypereosinophilia. In Molecular carcinogenesis, 59, 87-103. doi:10.1002/mc.23131. https://pubmed.ncbi.nlm.nih.gov/31691359/

6. Yang, Yiping, Zhou, Menghan, Huang, Yurun, Huang, Yi, Wang, Shan. 2024. LCP1-mediated cytoskeleton alterations involve in arsenite-triggered malignant phenotype of human immortalized prostate stromal cells. In Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 186, 114548. doi:10.1016/j.fct.2024.114548. https://pubmed.ncbi.nlm.nih.gov/38417537/