Abstract
Protein degradation by lysosomes and proteasomes is regulated by a dynamic equilibrium between ubiquitination apd deubiquitination enzymes. As protein turnover is key to regulating cellular function, particularly in highly specialized or polarized cells such as neurons, the effects of both enzyme sets can be profound with regard to synaptic plasticity and development. At the synapse, increased ubiquitination has been found to increase endocytic removal of transmembrane receptors such as mammalian AMP A or nematode GLR-1 glutamate receptors, which are then sorted either for recycling or degradation. It is unclear if this mechanism is functionally conserved between invertebrates and mammals, but it is believed that mammalian receptors are regulated by ubiquitination of their associated scaffolding proteins while yeast and nematodes display direct ubiquitination of transmembrane receptors. The deubiquitination pathway is less well characterized, but preliminary evidence suggests that nematode deubiquitinating enzyme usp-46 may regulate glutamate receptor accumulation. Here, we sought to 1 determine if a knock-down of the mammalian homo1ogs of nematode usp-46, USP 12 and USP46, in cultured rat hippocampal neurons causes a decreased abundance of either synaptic or extra-synaptic AMP A receptors.