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J Biol Chem, Vol. 274, Issue 12, 7952-7957, March 19, 1999

Regulation of -Amyloid Secretion by FE65, an Amyloid Protein Precursor-binding Protein

Shasta L. Sabo, Lorene M. Lanier, Annat F. Ikin, Olga Khorkova^§, Sudhir Sahasrabudhe^§, Paul Greengard, and Joseph D. Buxbaum^¶

From the  Laboratory of Molecular and Cellular Neuroscience and Zachary and Elizabeth M. Fisher Center, The Rockefeller University, New York, New York 10021, the ^§ Biotechnology Group, Hoechst Marion Roussel, Bridgewater, New Jersey 08807, and the ^¶ Laboratory of Molecular Neuropsychiatry, Departments of Psychiatry and Neurobiology, Mount Sinai School of Medicine, New York, New York 10029

The principal component of Alzheimer's amyloid plaques, A, derives from proteolytic processing of the Alzheimer's amyloid protein precursor (APP). FE65 is a brain-enriched protein that binds to APP. Although several laboratories have characterized the APP-FE65 interaction in vitro, the possible relevance of this interaction to Alzheimer's disease has remained unclear. We demonstrate here that APP and FE65 co-localize in the endoplasmic reticulum/Golgi and possibly in endosomes. Moreover, FE65 increases translocation of APP to the cell surface, as well as both APP_s and A secretion. The dramatic (4-fold) FE65-dependent increase in A secretion suggests that agents which inhibit the interaction of FE65 with APP might reduce A secretion in the brain and therefore be useful for preventing or slowing amyloid plaque formation.

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Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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