First Author | Hoareau C | Year | 2008 |
Journal | Neurobiol Aging | Volume | 29 |
Issue | 4 | Pages | 542-53 |
PubMed ID | 17169463 | Mgi Jnum | J:135033 |
Mgi Id | MGI:3790274 | Doi | 10.1016/j.neurobiolaging.2006.11.012 |
Citation | Hoareau C, et al. (2008) Amyloid precursor protein cytoplasmic domain antagonizes reelin neurite outgrowth inhibition of hippocampal neurons. Neurobiol Aging 29(4):542-53 |
abstractText | The function of the amyloid precursor protein (APP), a key molecule in Alzheimer's disease (AD) remains unknown. Among the proteins that interact with the APP cytoplasmic domain in vitro and in heterologous systems is Disabled-1, a signaling molecule of the reelin pathway. The physiological consequence of this interaction is unknown. Here we used an in vitro model of hippocampal neurons grown on a reelin substrate that inhibits neurite outgrowth. Our results show that an excess of APP cytoplasmic domain internalized by a cell permeable peptide, is able to antagonize the neurite outgrowth inhibition of reelin. The APP cytoplasmic domain binds Disabled-1 and retains it in the cytoplasm, preventing it from reaching the plasma membrane and sequesters tyrosine phosphorylated Disabled-1, both of which disrupt reelin signaling. In the context of AD, increased formation of APP cytoplasmic domain in the cytosol released after cleavage of the A beta peptide, could then inhibit reelin signaling pathway in the hippocampus and thus influence synaptic plasticity. |