Local mRNA translation is likely to have a rapid and pronounced effect on axonal function because it results in a rapid and highly localized increase in the level of specific proteins.  However, in order for successive stimuli to continue to exert effects on axons, the levels of the proteins have to return to baseline levels.  One likely mechanism that functions to turn off the effect of local synthesis is local protein ubiquitination.  Indeed, axons contain the machinery required to ubiquitinate and degrade proteins.  

Currently, there are no simple techniques to survey cells for proteins that are ubiquitinated in response to specific signals.  Additionally, there is no way to screen for proteins that are regulated by specific ubiquitin ligase enzymes.  Since the human genome encodes over 500 ubiquitin ligases, determining their specificity would have considerable impact for understanding signaling in cells as well as for identifying valuable targets for therapeutic intervention.

We are developing novel chemical approaches that allow ubiquitinated proteins to be rapidly identified and quantified using high-throughput mass spectrometry.  These techniques will provide fundamentally new methods for studying ubiquitination in cells, and will also allow us to probe the roles of ubiquitination in axonal signaling.