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Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain
Published on: August 28, 2012
Calreticulin functions as a molecular chaperone for the beta-amyloid precursor protein
R J Johnson1, G Xiao, J Shanmugaratnam
1Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA. rjohnson@bu.edu
Neurobiology of Aging
|May 30, 2001
Summary
Beta-amyloid precursor protein (APP) interacts with calreticulin (Crt) during its maturation in the endoplasmic reticulum and Golgi. This transient interaction is crucial for glycoprotein quality control in Alzheimer's disease pathogenesis.
Area of Science:
- Cell Biology
- Neuroscience
- Biochemistry
Background:
- Beta-amyloid precursor protein (APP) processing is implicated in Alzheimer's disease pathogenesis.
- Chaperone proteins, like calreticulin (Crt), are vital for glycoprotein maturation.
- Understanding APP-chaperone interactions is key to elucidating APP processing pathways.
Purpose of the Study:
- To investigate the interaction between calreticulin (Crt) and beta-amyloid precursor protein (APP).
- To determine the physiological significance of Crt-APP interaction in APP maturation and quality control.
Main Methods:
- Studied the binding of Crt and APP under varying pH and divalent cation conditions.
- Investigated the role of N-linked glycosylation in the Crt-APP interaction.
- Analyzed the association of immature and mature APP with protein complexes.
Main Results:
- APP exhibits transient binding to Crt, dependent on pH, divalent cations, and N-linked glycosylation.
- Both immature and mature APP forms bind to Crt.
- Immature APP is largely associated with protein complexes, while mature APP shows minimal association.
Conclusions:
- The interaction between APP and Crt is physiologically significant for APP maturation.
- Crt plays a role in the quality control of nascent glycoproteins within the secretory pathway.
- This interaction may offer insights into therapeutic strategies for Alzheimer's disease by targeting APP processing.
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