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First published online 13 February 2008
doi: 10.1242/dev.007401

Development 135, 1189-1199 (2008)
Published by The Company of Biologists 2008
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Interaction of amyloid precursor protein with contactins and NgCAM in the retinotectal system

Miriam Osterfield, Rikke Egelund, Lauren M. Young and John G. Flanagan*

Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.

* Author for correspondence (e-mail: flanagan{at}hms.harvard.edu)

Accepted 9 January 2008

The amyloid precursor protein (APP) plays a central role in Alzheimer's disease, but its actions in normal development are not well understood. Here, a tagged APP ectodomain was used to identify extracellular binding partners in developing chick brain. Prominent binding sites were seen in the olfactory bulb and on retinal axons growing into the optic tectum. Co-precipitation from these tissues and tandem mass spectrometry led to the identification of two associated proteins: contactin 4 and NgCAM. In vitro binding studies revealed direct interactions among multiple members of the APP and contactin protein families. Levels of the APP processing fragment, CTF{alpha}, were modulated by both contactin 4 and NgCAM. In the developing retinotectal system, APP, contactin 4 and NgCAM are expressed in the retina and tectum in suitable locations to interact. Functional assays revealed regulatory effects of both APP and contactin 4 on NgCAM-dependent growth of cultured retinal axons, demonstrating specific functional interactions among these proteins. These studies identify novel binding and functional interactions among proteins of the APP, contactin and L1CAM families, with general implications for mechanisms of APP action in neural development and disease.

Key words: Amyloid precursor protein, Axon, Contactin, L1CAM, Retina






© The Company of Biologists Ltd 2008