Table 1.
List of E3 ligases involved in the processes of neural development
| UPS component | Mechanism of action | References |
|---|---|---|
| Neural stem and progenitor cells | ||
| SCF-bTRCP | REST/NSFR is a master repressor of neural gene expression; SCF-bTRCP is responsible for UPS-mediated REST degradation, allowing derepression of pro-neural REST targets | [50] |
| HUWE1 | HUWE1 supression of a N-Myc-DLL3 cascade, setting cell-cycle withdrawal and neuronal differentiation, restrains proliferation and enables neuronal differentiation | [53] |
| BTBD6 | BTBD6 acts as an adaptor protein in the SCF E3 ligase complex and targets the transcriptional repressor and neurogenesis inhibitor Plzf for degradation | [54] |
| MIB1 | RING-type E3 MIB1 expressing cells generate Notch signaling in neighboring radial glial cells to maintain their stemness and correct differentiation | [52] |
| TRIM11 | TRIM11 mediates the degradation of the development regulator transcription factor Pax6 | [51] |
| Neural cell migration | ||
| E3 ligase complex containing cullin 5 | Cul5 auxiliates Dab1 dgradation in target neurons after a signaling cascade that involves VLDR and ApoE receptors, directing the speed and correct migration of neuronal populations | [55, 56] |
| Axonal growth | ||
| RPM-1 | RPM-1 E3 ligase negatively regulates axon outgrowth by the guidance receptors SAX-3/robo and UNC-5/UNC-5 | [78] |
| CDH1-APC complex | Ubiquitin ligase CDH1-APC operates in the nucleus of neurons to inhibit axon growth through the promotion of transcription factors SnoN and Id2 degradation | [58, 59] |
| NEDD4 | NEDD4 acts as a positive regulator of dendrite extension and arborization through the ubiquitination of RAP2A and PTEN downregulation | [61, 62] |
| SMURF1 | SMURF1 enhances neurite outgrowth ubiquitinating RhoA | [57] |
| SMURF2 | SMURF2 ubiquitinates RAP1B directing it to proteasomal degradation, assuring that only one neurite will become an axon | [60] |
| Synaptic pruning | ||
| DIAP1 | E3 ligase DIAP1 degradation, mediated by UBCD1 conjugating enzyme, leads to a caspase-dependent efficient pruning of the C4da neuron in Drosophila | [65] |
| RPM-1 | RPM-1 E3 ligase negatively regulates a p38 MAPK pathway contibuting to the correct formation of mature synapses in C. elegans | [64] |
| SKR1 | SKR-1, a core component of SCF E3, contributes to synapse elimination in a proteasome-dependent manner in HSNL | [66] |