| First Author | Rama N | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 35 | Pages | 30014-23 |
| PubMed ID | 22782894 | Mgi Jnum | J:190417 |
| Mgi Id | MGI:5448808 | Doi | 10.1074/jbc.M111.324780 |
| Citation | Rama N, et al. (2012) Amyloid precursor protein regulates netrin-1-mediated commissural axon outgrowth. J Biol Chem 287(35):30014-23 |
| abstractText | The multifunctional protein netrin-1 was initially discovered as the main attractive cue for commissural axon guidance by acting through its receptor DCC. Recently, we have shown that netrin-1 also interacts with the orphan transmembrane receptor amyloid precursor protein (APP). APP is cleaved by proteases, generating amyloid-beta peptide, the main component of the amyloid plaques that are associated with Alzheimer disease. Our previous work demonstrated that via its interaction with APP, netrin-1 is a negative regulator of amyloid-beta production in adult brain, but the biological relevance of APP/netrin-1 interaction under non-pathological conditions was unknown. We show here that during commissural axon navigation, APP, expressed at the growth cone, is part of the DCC receptor complex mediating netrin-1-dependent axon guidance. APP interacts with DCC in the presence of netrin-1 and enhances netrin-1-mediated DCC intracellular signaling, such as MAPK activation. Inactivation of APP in mice is associated with reduced commissural axon outgrowth. Thus, APP functionally acts as a co-receptor for DCC to mediate axon guidance. |
