Secreted APP regulates the function of full-length APP in neurite outgrowth through interaction with integrin beta1

Neural Development - Tập 3 Số 1 - 2008
Tracy L. Young‐Pearse1, Allen Ching-Way Chen1, Rui B. Chang1, César Márquez1, Dennis J. Selkoe1
1Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA

Tóm tắt

Abstract Background β-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-α) 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-α, the principal cleavage product of APP, also undergo neurite elongation. However, APPs-α is unable to stimulate neurite elongation in the absence of cellular APP expression. The outgrowth-enhancing effects of both APPs-α and the deletion of APP are inhibited by blocking antibodies to Integrin β1 (Itgβ1). Moreover, full length APP interacts biochemically with Itgβ1, and APPs-α can interfere with this binding. Conclusion Our findings indicate that APPs-α regulates the function of APP in neurite outgrowth via the novel mechanism of competing with the binding of APP to Itgβ1.

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Neural Development

Tập 3 Số 1

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