Cell-type-specific proteomics in the in vivo mouse brain

Krogager, T.P. et al. Nat. Biotechnol. https://doi.org/10.1038/nbt.4056 (2017).

Orthogonal tRNA synthetase-tRNA pairs have been used to tag proteins during translation in a variety of contexts ranging from microbes to cell culture and flies. Krogager et al. have adapted the pyrrolysyl-tRNA synthetase-tRNA_CAU system to analyze proteomes in the mouse brain in a cell-type-specific manner. The researchers deliver the tool with adeno-associated viruses (AAVs) and achieve cell-type specificity by using neuronal or glial promoters for tRNA synthetase expression. They also generated a Cre-dependent version of the AAV to allow further restriction of the expression pattern. After labeling of the nascent proteome, the tagged proteins can be either visualized or enriched and analyzed by mass spectrometry. The researchers applied their approach to analyze the proteome of neurons in the mouse striatum.