Expanding the Genetic Code for Neuronal Studies

Genetic code expansion is one of the most powerful technologies in protein engineering. In addition to the 20 canonical amino acids, the expanded genetic code is supplemented by unnatural amino acids, which have artificial side chains that can be introduced into target proteins in vitro and in vivo. A wide range of chemical groups have been incorporated co-translationally into proteins in single cells and multicellular organisms by using genetic code expansion. Incorporated unnatural amino acids have been used for novel structure-function relationship studies, bioorthogonal labelling of proteins in cellulo for microscopy and in vivo for tissue-specific proteomics, the introduction of post-translational modifications and optical control of protein function, to name a few examples. In this Minireview, the development of genetic code expansion technology is briefly introduced, then its applications in neurobiology are discussed, with a focus on studies using mammalian cells and mice as model organisms.