| First Author | Li J | Year | 2009 |
| Journal | Curr Biol | Volume | 19 |
| Issue | 24 | Pages | 2091-6 |
| PubMed ID | 19962314 | Mgi Jnum | J:156720 |
| Mgi Id | MGI:4421264 | Doi | 10.1016/j.cub.2009.10.039 |
| Citation | Li J, et al. (2009) Cytoplasmic ATM in neurons modulates synaptic function. Curr Biol 19(24):2091-6 |
| abstractText | ATM is a PI 3-kinase involved in DNA double-strand break repair. ATM deficiency leads to ataxia-telangiectasia (A-T), a syndrome of cancer susceptibility, hypersensitivity to ionizing radiation, immune deficiency, and sterility [1, 2]-phenotypes that can straightforwardly be attributed to a defective response to DNA damage. Yet patients with A-T also suffer from ataxia, speech defects, and abnormal body movements [3-5]-neurological phenotypes whose origins remain largely unexplained. Compounding the discordance, Atm mutations in mouse interfere with DNA repair but have only mild neurological symptoms [6-9], suggesting that the link between DNA damage and the death of neurons can be broken [10-12]. We find that in neurons, ATM protein has a substantial cytoplasmic distribution. We show that in Atm(tm1Awb) mice, hippocampal long-term potentiation is significantly reduced, as is the rate of spontaneous vesicular dye release, suggesting a functional importance of cytoplasmic ATM. In the cytoplasm, ATM forms a complex with two synaptic vesicle proteins, VAMP2 and synapsin-I, both of which must be phosphorylated to bind ATM. Also, cytoplasmic ATM physically associates with the homologous PI 3-kinase, ATR. The neurological symptoms of ataxia-telangiectasia may thus result from defective nonnuclear functions of ATM not associated with DNA repair. |
