| First Author | Kuljis RO | Year | 1999 |
| Journal | Brain Res | Volume | 842 |
| Issue | 2 | Pages | 351-8 |
| PubMed ID | 10526131 | Mgi Jnum | J:58022 |
| Mgi Id | MGI:1346372 | Doi | 10.1016/s0006-8993(99)01813-2 |
| Citation | Kuljis RO, et al. (1999) ATM immunolocalization in mouse neuronal endosomes: implications for ataxia-telangiectasia. Brain Res 842(2):351-8 |
| abstractText | Ataxia-telangiectasia (A-T) is a human disorder with pleiotropic manifestations that include neoplasms, immune dysfunction and neurodegeneration. The disorder is due to mutations in the gene known as ATM (A-T, mutated), which causes a deficiency in its protein product (Atm in mice) that is necessary for DNA damage surveillance. This nuclear function of Atm explains in principle the propensity to cancer and immunodeficiency in A-T, but not the neurodegeneration which results in the earliest clinical manifestations and causes progressive disability. Here we report ultrastructural evidence of cytoplasmic localization of Atm-like immunoreactivity (ALI) within endosomes in murine cerebellocortical neurons, one of the principal targets of A-T. The ALI was obtained with two separate monoclonal antibodies that recognize Atm specifically. By contrast, electron-dense endosomes that could be confused with ALI occur in negligible amounts in both wild-type mice and in mice deficient in Atm ('knockout' mice). Furthermore, there was a marked preferential distribution of Atm-immunopositive endosomes in the granule cell layer - where they are present in granule neurons - with a much lower density in the Purkinje and molecular layers. These observations suggest that endosome-bound Atm may be more important for the function of certain neurons than others - or that it is processed differently among them - and that this protein may be involved in molecular sorting in the cytoplasm. This is relevant to elucidating the role of Atm deficiency in the pathobiology of neurodegeneration in A-T. |
