Alvarez-Castelao, B. et al. Nat. Biotechnol. 35, 1196–1201 (2017).

Methods for tagging newly synthesized proteins allow researchers to fish proteins out from cells for identification using techniques such as mass spectrometry. The mutant methionyl-tRNA synthetase (MetRS) system allows methionine tRNA to be charged with the unnatural amino acid analog azidonorleucine, which contains a bioorthogonal moiety that can be tagged via click chemistry with a purification handle. By combining this technique with cell-type-specific promoters, it is possible to identify nascent proteins in specific classes of cells. Alvarez-Castelao et al. developed a transgenic mouse line to perform in vivo cell-type-specific nascent protein labeling experiments using Cre recombinase to induce expression of the mutant MetRS in specific cell types. With this approach, the researchers analyzed protein expression in excitatory principle neurons and in Purkinje neurons.