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-amyloid molecules linked to the pathogenesis of Alzheimer's disease. Since chaperone molecules such as calreticulin (Crt) have been shown to be important 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 immature APP (containing only N-linked sugars) and mature APP (containing both N-linked and O-linked sugars) bind to Crt. Both proteins are part of a complex 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 secretory pathway.
Johnson
R J
RJ
Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA. rjohnson@bu.edu
Xiao
G
G
Shanmugaratnam
J
J
Fine
R E
RE
D000544:Alzheimer Disease / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D037282:Calreticulin; D002413:Cations, Divalent / Q000378:metabolism; D002460:Cell Line; D003432:Cross-Linking Reagents; D003902:Detergents / Q000494:pharmacology; D006031:Glycosylation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D046911:Macromolecular Substances; D018832:Molecular Chaperones / Q000378:metabolism*; D008970:Molecular Weight; D011233:Precipitin Tests; D011485:Protein Binding / Q000187:drug effects; D012261:Ribonucleoproteins / Q000378:metabolism*; D014461:Ultracentrifugation
D016564:Amyloid beta-Protein Precursor; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D002413:Cations, Divalent; D003432:Cross-Linking Reagents; D003902:Detergents; D046911:Macromolecular Substances; D018832:Molecular Chaperones; D012261:Ribonucleoproteins