| First Author | Ramaker JM | Year | 2013 |
| Journal | J Neurosci | Volume | 33 |
| Issue | 24 | Pages | 10165-81 |
| PubMed ID | 23761911 | Mgi Jnum | J:199160 |
| Mgi Id | MGI:5500968 | Doi | 10.1523/JNEUROSCI.1146-13.2013 |
| Citation | Ramaker JM, et al. (2013) Amyloid precursor proteins interact with the heterotrimeric G protein Go in the control of neuronal migration. J Neurosci 33(24):10165-81 |
| abstractText | Amyloid precursor protein (APP) belongs to a family of evolutionarily conserved transmembrane glycoproteins that has been proposed to regulate multiple aspects of cell motility in the nervous system. Although APP is best known as the source of beta-amyloid fragments (Abeta) that accumulate in Alzheimer's disease, perturbations affecting normal APP signaling events may also contribute to disease progression. Previous in vitro studies showed that interactions between APP and the heterotrimeric G protein Goalpha-regulated Goalpha activity and Go-dependent apoptotic responses, independent of Abeta. However, evidence for authentic APP-Go interactions within the healthy nervous system has been lacking. To address this issue, we have used a combination of in vitro and in vivo strategies to show that endogenously expressed APP family proteins colocalize with Goalpha in both insect and mammalian nervous systems, including human brain. Using biochemical, pharmacological, and Bimolecular Fluorescence Complementation assays, we have shown that insect APP (APPL) directly interacts with Goalpha in cell culture and at synaptic terminals within the insect brain, and that this interaction is regulated by Goalpha activity. We have also adapted a well characterized assay of neuronal migration in the hawkmoth Manduca to show that perturbations affecting APPL and Goalpha signaling induce the same unique pattern of ectopic, inappropriate growth and migration, analogous to defective migration patterns seen in mice lacking all APP family proteins. These results support the model that APP and its orthologs regulate conserved aspects of neuronal migration and outgrowth in the nervous system by functioning as unconventional Goalpha-coupled receptors. |
