Development (2015)

A fundamental strategy used to study the function of proteins in a complex biological system is to make them ‘appear’ and ‘disappear’ at will, and then analyse the consequences. Conditional expression in eukaryotes is relatively easy, but controlled and targeted depletion is difficult to achieve. To this end, Abby Dernburg at the Lawrence Berkeley National Laboratory and colleagues transferred the plant auxin perception system into living nematodes.

Auxin receptors such as TIR1 connect auxin perception with the protein ubiquitination pathway. In the presence of auxin, TIR1 recognizes a degradation sequence (degron) in Aux/IAA transcriptional regulators. Non-plant eukaryotes do not have an auxin receptor, but do contain the ubiquitination machinery. Introducing a high-affinity version of Arabidopsis thaliana TIR1 and a small degron from IAA17 into Caenorhabditis elegans caused auxin-dependent degradation of several worm proteins.

The effect is fast, specific and, importantly, reversible. The strategy works during various developmental stages, for both cytoplasmic and nuclear proteins, and can be made tissue-specific. Auxin, as an inducer, is a small non-toxic molecule that easily diffuses through membranes. The system results in more penetrant phenotypes than RNAi and allows precise timing of degradation, all with minimal side effects. It is likely that we may soon see auxin vials in worm labs.