ArticleJournal of Alzheimer's disease : JAD2019
Dual Bioorthogonal Labeling of the Amyloid-β Protein Precursor Facilitates Simultaneous Visualization of the Protein and Its Cleavage Products.
Article in Journal of Alzheimer's disease : JAD, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- Bioorthogonal Chemistry in Neurobiology: From Imaging to Proteomics.Chembiochem : a European journal of chemical biology · 2026Review
- Noncanonical Amino Acid Tools and Their Application to Membrane Protein Studies.Chemical reviews · 2024Review
- Engineering Pyrrolysine Systems for Genetic Code Expansion and Reprogramming.Chemical reviews · 2024Review
- Bioorthogonal Reactions in Bioimaging.Topics in current chemistry (Cham) · 2024Review
- Bioorthogonal Tethering Enhances Drug Fragment Affinity for G Protein-Coupled Receptors in Live Cells.Journal of the American Chemical Society · 2023Article
- Molecular probes for cellular imaging of post-translational proteoforms.RSC chemical biology · 2022Review
- Minimal genetically encoded tags for fluorescent protein labeling in living neurons.Nature communications · 2022Article
- Deciphering the Structure and Formation of Amyloids in Neurodegenerative Diseases With Chemical Biology Tools.Frontiers in chemistry · 2022Review
- Engineered Human Induced Pluripotent Cells Enable Genetic Code Expansion in Brain Organoids.Chembiochem : a European journal of chemical biology · 2021Article
- New strategies for fluorescently labeling proteins in the study of amyloids.Current opinion in chemical biology · 2021Review
- A Genetic Code Expansion-Derived Molecular Beacon for the Detection of Intracellular Amyloid-β Peptide Generation.Angewandte Chemie (International ed. in English) · 2021Article
- A Genetic Code Expansion-Derived Molecular Beacon for the Detection of Intracellular Amyloid-β Peptide Generation.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2021Article
- Using unnatural amino acids to selectively label proteins for cellular imaging: a cell biologist viewpoint.The FEBS journal · 2021Review
- Expanding the Genetic Code for Neuronal Studies.Chembiochem : a European journal of chemical biology · 2020Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The amyloid-β protein precursor (AβPP) is critical in the pathophysiology of Alzheimer's disease (AD), since two-step proteolytic processing of AβPP generates the neurotoxic amyloid-β peptide (Aβ). We developed a dual fluorescence labeling system to study the exact subcellular location of γ-secretase cleavage of AβPP. The C-terminal tail of AβPP was fluorescently labeled using a SNAP-tag, while the Aβ region of AβPP was fluorescently tagged with a dye at a genetically-encoded noncanonical amino acid (ncAA). The ncAA was introduced at specific positions in AβPP using a genetic code expansion strategy and afterwards, the reactive side-chain of the ncAA was coupled to the dye using a bioorthogonal labeling chemistry. In proof-of-concept experiments, HEK293T cells were transfected with plasmids containing engineered AβPP harboring an amber mutation and an amber codon suppression system with an evolved tRNA synthetase/tRNA pair and grown in the presence of a lysine-derived ncAA. Processing of the AβPP variants was validated with ELISA and immunoblotting, and seven AβPP mutants that showed similar cleavage pattern as wild-type AβPP were identified. The AβPP mutant was fluorescently labeled with 6-methyl-tetrazine-BDP-FL and TMR-Star at the ncAA and SNAP-tag, respectively. Using this approach, AβPP was fluorescently labeled at two sites in living cells with minimal background to allow monitoring of Aβ and C-terminal cleavage products simultaneously. The method described provides a powerful tool to label Aβ with minimal perturbations of its processing, thus enabling studies of the trafficking of the cleavage products of AβPP.
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