Atat1, also known as α-tubulin acetyltransferase 1, is an enzyme responsible for lysine 40 acetylation on α-tubulin across various species from protists to mammals [1]. This acetylation is associated with long-lived stable microtubules, which are more resistant to mechanical breakdown, and is involved in multiple cellular activities like cell motility, mitosis, cytoskeletal organization, and intracellular trafficking [1]. Genetic models, such as gene knockout mouse models, have been crucial in understanding its in-vivo functions.

In Atat1 knockout mice, starting from postnatal day 5, there are enlarged lateral ventricles in the forebrain due to hypoplasia in the septum and striatum, along with deficits in motor coordination, indicating its importance in forebrain development [2]. Also, in these mice, neuronal migration to the septum and striatum is impaired during brain development, and there are mild defects in cell proliferation and primary cilium formation in mutant embryonic fibroblasts [2]. Additionally, ATAT1 deficiency enhances microglia/macrophage-mediated erythrophagocytosis and hematoma absorption following intracerebral hemorrhage, suggesting its potential as a target for intracerebral hemorrhage treatment [3].

In conclusion, Atat1 plays essential roles in microtubule acetylation, which is crucial for multiple cellular processes. Studies using Atat1 KO mouse models have revealed its significance in forebrain development and response to intracerebral hemorrhage, highlighting its potential as a therapeutic target in related disease areas.

References:

1. Iuzzolino, Angela, Pellegrini, Francesca Romana, Rotili, Dante, Degrassi, Francesca, Trisciuoglio, Daniela. 2024. The α-tubulin acetyltransferase ATAT1: structure, cellular functions, and its emerging role in human diseases. In Cellular and molecular life sciences : CMLS, 81, 193. doi:10.1007/s00018-024-05227-x. https://pubmed.ncbi.nlm.nih.gov/38652325/

2. Li, Lin, Jayabal, Sriram, Ghorbani, Mohammad, Watt, Alanna J, Yang, Xiang-Jiao. 2019. ATAT1 regulates forebrain development and stress-induced tubulin hyperacetylation. In Cellular and molecular life sciences : CMLS, 76, 3621-3640. doi:10.1007/s00018-019-03088-3. https://pubmed.ncbi.nlm.nih.gov/30953095/

3. Zhang, Yihua, Huang, Ping, Cao, Min, He, Xuzhi, Xu, Lunshan. . ATAT1 deficiency enhances microglia/macrophage-mediated erythrophagocytosis and hematoma absorption following intracerebral hemorrhage. In Neural regeneration research, 19, 1072-1077. doi:10.4103/1673-5374.382984. https://pubmed.ncbi.nlm.nih.gov/37862210/