Calreticulin functions as a molecular chaperone for the beta-amyloid precursor protein

Processing of the beta -amyloid precursor protein (APP) in the endoplasmic reticulum and the Golgi apparatus may be critical in generating the beta -a myloid molecules linked to the pathogenesis of Alzheimer's disease. Since c haperone molecules such as calreticulin (Crt) have been shown to be importa nt in the maturation of many glycoproteins, we investigated the interaction between Crt and APP. We show that APP binds transiently to Crt in a manner that is pH, divalent cation, and N-linked glycosylation-dependent. Both im mature APP (containing only N-linked sugars) and mature APP (containing bot h N-linked and O-linked sugars) bind to Crt. Both proteins are part of a co mplex that appears to be large enough to accommodate other proteins as well . However, while most of the immature form is associated with the complexes , very little of the mature form is. The interaction between APP and Crt is likely to be of physiological significance with respect to APP maturation since Crt is involved in quality control of nascent glycoproteins in the se cretory pathway. (C) 2001 Elsevier Science Inc. All rights reserved.