The role of ubiquitin-mediated pathways in regulating synaptic development, axonal degeneration and regeneration: insights from fly and worm.

The covalent attachment of the 76 amino acid peptide ubiquitin to target proteins is a rapid and reversible modification that regulates protein stability, activity and localization. As such, it is a potent mechanism for sculpting the synapse. Recent studies from two genetic model organisms, Caenorhabditis elegans and Drosophila, have provided mounting evidence that ubiquitin-mediated pathways play important roles in controlling the presynaptic size, synaptic elimination and stabilization, synaptic transmission, postsynaptic receptor abundance, axonal degeneration and regeneration. While the data supporting the requirement of ubiquitination/deubiquitination for normal synaptic development and repair are compelling, detailed analyses of signalling events up- and downstream of these ubiquitin modifications are often challenging. This article summarizes the related research conducted in worms and flies and provides insight into the fundamental questions facing this field.