| First Author | Young-Pearse TL | Year | 2008 |
| Journal | Neural Dev | Volume | 3 |
| Pages | 15 | PubMed ID | 18573216 |
| Mgi Jnum | J:160741 | Mgi Id | MGI:4454998 |
| Doi | 10.1186/1749-8104-3-15 | Citation | Young-Pearse TL, et al. (2008) Secreted APP regulates the function of full-length APP in neurite outgrowth through interaction with integrin beta1. Neural Dev 3:15 |
| abstractText | BACKGROUND: Beta-amyloid precursor protein (APP) has been reported to play a role in the outgrowth of neurites from cultured neurons. Both cell-surface APP and its soluble, ectodomain cleavage product (APPs-alpha) have been implicated in regulating the length and branching of neurites in a variety of assays, but the mechanism by which APP performs this function is not understood. RESULTS: Here, we report that APP is required for proper neurite outgrowth in a cell autonomous manner, both in vitro and in vivo. Neurons that lack APP undergo elongation of their longest neurite. Deletion of APLP1 or APLP2, homologues of APP, likewise stimulates neurite lengthening. Intriguingly, wild-type neurons exposed to APPs-alpha, the principal cleavage product of APP, also undergo neurite elongation. However, APPs-alpha is unable to stimulate neurite elongation in the absence of cellular APP expression. The outgrowth-enhancing effects of both APPs-alpha and the deletion of APP are inhibited by blocking antibodies to Integrin beta1 (Itgbeta1). Moreover, full length APP interacts biochemically with Itgbeta1, and APPs-alpha can interfere with this binding. CONCLUSION: Our findings indicate that APPs-alpha regulates the function of APP in neurite outgrowth via the novel mechanism of competing with the binding of APP to Itgbeta1. |
