Fig. 5.
A model of RNF121-mediated quality control of Nav channels. (A) A WT neuron wherein RNF121 mediates ubiquitination of misfolded NaV channels marking them for proteasome-mediated degradation. Properly folded NaV channels (green) associate with NaVβ subunits (magenta) in the Golgi apparatus and are transported to the AIS. Of note, some NaVβ subunits are transported to the membrane independent of NaV channels. (B) An rnf121 mutant neuron wherein misfolded NaV channels (red) accumulate in the ER and cis-Golgi compartments, which, over time, depletes NaVβ subunits, preventing them from forming complexes with properly folded NaV channels, causing an impairment of NaV transport.