Table 2.

List of E3 ligases involved in the regulation of post-synaptic function

E3 ligases	Mechanism of action	References
UBE3A	Neuronal activity promotes UBE3A expression and consequent downregulation of the substrate ARC, known to be involved in AMPAr endocytosis	[116, 118]
APC	APC E3 recruits CDC20 co-factor and regulates the abundance of GLR-1 receptors on the post-synaptic compartment in C. elegans; in Drosophila, APC/C is involved in the regulation of synaptic size in NMJ and also in the regulation of post-synaptic GluA2 levels	[96, 101, 131]
PDZRN3A	PDZRN3A synapse-associated RING finger E3 binds to MuSK and downregulates its surface levels, thus regulating the post-synaptic dvelopment of the NMJ	[273]
SCF/LIN23	SCF E3 containing F-box protein LIN-23 regulates GLR-1 abundance in C. elegans ventral cord through the ubiquitination of BAR-1	[103]
KEL-8/CUL3	KEL-8 binds CUL3 forming an E3 ubiquitin ligase complex that is required for synaptic removal of GLR-1 in C. elegans	[100]
RPM-1	RPM-1 forms an E3 SCF complex with FSN-1, SKR-1, and CUL-1; RPM-1 inhibits p30 MAPK signaling inducing GLR-1 endocytosis in C. elegans synapses	[102]
MDM2	MDM2 E3 ligase ubiquitinates the scaffolding protein PSD95 upon NMDA activation, leading to its proteasomal degradation, thus regulating AMPA receptors synaptic levels	[274]
FBX2/CHIP	FBX2, a component of SCF E3 ligase complex, binds CHIP E3, and the interaction facilitates GluN1/2 NMDA receptor subunit degradation	[275]
MIB2	MIB2 ubiquitinates GluN2A and NMDA receptor activity is downregulated by MIB2 in a ubiquitin proteasome-dependent manner	[276]
TRIM3	Upon neuronal activity, the RING finger-containing E3 TRIM3 promotes ubiquitination and proteasome-dependent degradation of the PSD protein GKAP acting as an inhibitor of dendritic spine growth in hippocampal neurons	[277]
SCRAPPER	SCRAPPER is the F-box component of a SCF E3; SCRAPPER ubiquitinates RIM-1 regulating its levels and controlling synaptic vesicle release	[93]