Fig. 5.

Schematic of the proposed function of NMP contribution to the maintenance of homeostasis of neuronal activity in response to elevated neuronal activity. A portion of the neuronal dendrite including a spine is exemplified under three different conditions (boxes): the basal condition (Left), the stimulated condition (Upper Right), and the stimulated condition in the presence of BE, which blocks NMP activity (Lower Right). NMPs are shown in the plasma membrane, ribosomes, nascent proteins (tan), preexisting proteins (blue), and the 26S proteasome, which carries out UPS-mediated protein degradation, are shown in the cytoplasm. Under basal conditions (Left), there is a low level of NMP-mediated degradation of nascent proteins, which are produced by either constitutive protein synthesis or from ongoing neural activity. Upon enhanced stimulation (Upper Right), protein synthesis increases, and the resultant nascent proteins contribute to activity-dependent synaptic plasticity mechanisms that strengthen synaptic connections and increase synaptic transmission. A significant proportion of these activity-induced plasticity-related nascent proteins is degraded by NMPs, which help to maintain neuronal activity within a normal range. Under the stimulated condition, when NMPs are inhibited by BE (Lower Right, BE: green and orange shape bound to NMPs), excess nascent proteins that were not degraded induce aberrant neuronal activity.