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Cell-selective Proteomics for Biological Discovery


Cell-selective Proteomics for Biological Discovery

Shannon E Stone et al. Curr Opin Chem Biol.


Cells alter the proteome to respond to environmental and developmental cues. Global analysis of proteomic responses is of limited value in heterogeneous environments, where there is no 'average' cell. Advances in sequencing, protein labeling, mass spectrometry, and data analysis have fueled recent progress in the investigation of specific subpopulations of cells in complex systems. Here we highlight recently developed chemical tools that enable cell-selective proteomic analysis of complex biological systems, from bacterial pathogens to whole animals.


Figure 1
Figure 1
The importance of cell-type-specific proteomics. Bulk measurements of complex tissues can obscure proteomic changes that occur in specific sub-populations of cells. A protein that is highly expressed (up arrows) in the cells of interest might be detected at low abundance overall due to low expression (down arrows) in background cells. Cells of interest must be physically isolated or tagged to measure the cell-specific proteome. Physical isolation measures steady-state levels of intracellular proteins, whereas labeling methods can be time-resolved and used to identify secreted proteins.
Figure 2
Figure 2
Labeling strategies for cell-selective proteomics. a) The process by which amino acids are incorporated into proteins, and the step exploited by each of the labeling methods discussed in this Opinion. b) Schematic of each technique. Translating ribosome affinity purification: TRAP; Cell type-specific labeling using amino acid precursors: CTAP; Bio-orthogonal non-canonical amino acid tagging: BONCAT; Stochastic orthogonal recoding of translation: SORT; O-propargyl puromycin: OP-Puro; ascorbate peroxidase: APEX; Lysine racemase:Lyr; diaminopimelate decarboxylase: DDC; aminoacyl-tRNA synthetase: RS; penicillin-G-acylase: PGA.

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