Fig 9. A schematic model depicting USP6-dependent regulation of synaptic function.

The hominoid-specific gene USP6 is required for maintaining synaptic function by stabilizing NMDARs. USP6 deubiquitinates NMDAR at the PSD, thereby facilitating NMDAR stabilization, resulting in increased NMDAR function and synaptic activity and enhanced cognition. AMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; LTP, long-term potentiation; NMDAR, N-methyl-D-aspartate-type glutamate receptor; PSD, postsynaptic density; USP, ubiquitin-specific protease.