Abl2, also known as ABL-related gene (Arg), is a member of the Abelson family of non-receptor tyrosine kinases. It plays essential roles in regulating cell migration, morphogenesis, and cytoskeletal reorganization. It is involved in pathways related to axon guidance, neuronal morphogenesis, and synaptic function in the nervous system. In cancer, it has been associated with processes like cell adhesion, metastasis, and chemotherapy resistance [2,3,4,5]. Genetic models, such as knockout mice, have been valuable in studying its functions.

In mice, Abl2 knockout leads to various phenotypic changes. Abl2-deficient COS-7 cells show slowed microtubule reassembly after nocodazole treatment, indicating its role in microtubule regulation, as Abl2 promotes microtubule nucleation and repair through interactions with tubulin and the microtubule lattice [1]. In neurons, disruption of Abl2 compromises dendritic spine stability and size by eliminating the small pool of stable actin filaments required for spine stability [4]. Abl2 knockout mice also exhibit anxiety-like and depressive-like behaviors, with proteomic analysis of the hippocampus highlighting alterations in proteins related to these behaviors, especially those associated with the GABAergic synapse [6]. In medulloblastoma, knockdown of Abl2 decreases cell adhesion to the extracellular matrix and tumor burden in a mouse model, suggesting its role in leptomeningeal dissemination [5].

In conclusion, Abl2 is crucial for multiple biological functions including microtubule regulation, dendritic spine stability, and emotional behaviors. Its role in diseases like medulloblastoma and potential implications in other cancers, as revealed by knockout mouse models, makes it an important target for further research. Understanding Abl2 could provide new insights into the mechanisms of these diseases and potentially lead to novel therapeutic strategies.

References:

1. Duan, Daisy, Lyu, Wanqing, Chai, Pengxin, Zhang, Kai, Koleske, Anthony J. 2023. Abl2 repairs microtubules and phase separates with tubulin to promote microtubule nucleation. In Current biology : CB, 33, 4582-4598.e10. doi:10.1016/j.cub.2023.09.018. https://pubmed.ncbi.nlm.nih.gov/37858340/

2. Kabirova, M, Reichenstein, M, Borovok, N, Gorobets, D, Michaelevski, I. 2023. Abl2 Kinase Differentially Regulates iGluRs Current Activity and Synaptic Localization. In Cellular and molecular neurobiology, 43, 2785-2799. doi:10.1007/s10571-023-01317-9. https://pubmed.ncbi.nlm.nih.gov/36689065/

3. Tasian, Sarah K, Loh, Mignon L, Hunger, Stephen P. 2017. Philadelphia chromosome-like acute lymphoblastic leukemia. In Blood, 130, 2064-2072. doi:10.1182/blood-2017-06-743252. https://pubmed.ncbi.nlm.nih.gov/28972016/

4. Shaw, Juliana E, Kilander, Michaela B C, Lin, Yu-Chih, Koleske, Anthony J. 2021. Abl2:Cortactin Interactions Regulate Dendritic Spine Stability via Control of a Stable Filamentous Actin Pool. In The Journal of neuroscience : the official journal of the Society for Neuroscience, 41, 3068-3081. doi:10.1523/JNEUROSCI.2472-20.2021. https://pubmed.ncbi.nlm.nih.gov/33622779/

5. Jones, Jill K, Zhang, Hengshan, Lyne, Anne-Marie, Pendergast, Ann Marie, Thompson, Eric M. 2023. ABL1 and ABL2 promote medulloblastoma leptomeningeal dissemination. In Neuro-oncology advances, 5, vdad095. doi:10.1093/noajnl/vdad095. https://pubmed.ncbi.nlm.nih.gov/37781087/

6. Yao, Xiaojuan, Chen, Ruiying, Chen, Hongting, Koleske, Anthony, Xiao, Xiao. 2024. Impact of Abl2/Arg deficiency on anxiety and depressive behaviors in mice. In Behavioural brain research, 468, 115022. doi:10.1016/j.bbr.2024.115022. https://pubmed.ncbi.nlm.nih.gov/38697301/