G3bp2, short for Ras-GAP SH3 domain binding protein 2, is an RNA-binding protein. Its protein structure enables it to bind with RNA or protein, regulating the nucleoplasmic shuttle. It participates in diverse biological functions such as cell growth, differentiation, migration, and RNA and protein metabolism, and is involved in pathways related to stress granule formation [1].

A G3bp2 conditional knockout (cKO) mouse model was generated to explore its role in male fertility. The cKO male mice were fertile with normal testis and sperm morphology, similar sperm concentration and motility. However, there was increased germ-cell apoptosis in their testes, indicating that G3BP2 is dispensable for spermatogenesis and male fertility in mice despite the increased apoptosis [5]. In G3bp2 -/- Apoe -/- mice, atherosclerotic lesions were significantly decreased as G3BP2 deficiency protected endothelial barrier function, decreased monocyte adhesion to endothelial cells, and inhibited pro-inflammatory cytokine levels. Loss of G3BP2 also diminished oscillatory shear stress-induced inflammation in endothelial cells, suggesting G3BP2 is a critical gene in regulating endothelial cell function [4]. Knockdown of G3BP2 in human neurons and brain organoids led to a significant elevation of Tau pathology, as G3BP2 directly interacts with Tau and inhibits its aggregation, playing a role as a defense against Tau aggregation in tauopathies [2]. In non-small cell lung cancer (NSCLC), knockdown of G3BP2 reduced the proliferation and migration of NSCLC cells, showing its role in cancer progression [3].

In summary, G3bp2 is involved in multiple biological processes. The use of G3bp2 KO/CKO mouse models has revealed its dispensability in spermatogenesis and male fertility, while highlighting its significance in diseases like atherosclerosis, tauopathies, and NSCLC. These models have provided valuable insights into the role of G3bp2 in specific biological processes and disease conditions, contributing to a better understanding of related pathologies and potential therapeutic strategies.

References:

1. Jin, Ge, Zhang, Zhen, Wan, Jingjing, Liu, Xia, Zhang, Weidong. 2022. G3BP2: Structure and function. In Pharmacological research, 186, 106548. doi:10.1016/j.phrs.2022.106548. https://pubmed.ncbi.nlm.nih.gov/36336216/

2. Wang, Congwei, Terrigno, Marco, Li, Juan, Grüninger, Fiona, Jagasia, Ravi. 2023. Increased G3BP2-Tau interaction in tauopathies is a natural defense against Tau aggregation. In Neuron, 111, 2660-2674.e9. doi:10.1016/j.neuron.2023.05.033. https://pubmed.ncbi.nlm.nih.gov/37385246/

3. Li, Haichang, Lin, Pei-Hui, Gupta, Pranav, Merritt, Robert E, Ma, Jianjie. 2021. MG53 suppresses tumor progression and stress granule formation by modulating G3BP2 activity in non-small cell lung cancer. In Molecular cancer, 20, 118. doi:10.1186/s12943-021-01418-3. https://pubmed.ncbi.nlm.nih.gov/34521423/

4. Li, Tianhan, Qiu, Juhui, Jia, Tingting, Chen, Yaokai, Wang, Guixue. 2021. G3BP2 regulates oscillatory shear stress-induced endothelial dysfunction. In Genes & diseases, 9, 1701-1715. doi:10.1016/j.gendis.2021.11.003. https://pubmed.ncbi.nlm.nih.gov/36157502/

5. Yun, Damin, Zhou, Liwei, Shi, Jie, Wu, Xiaolong, Sun, Fei. 2022. G3BP2, a stress granule assembly factor, is dispensable for spermatogenesis in mice. In PeerJ, 10, e13532. doi:10.7717/peerj.13532. https://pubmed.ncbi.nlm.nih.gov/35782098/