Table 1.
Ubiquitin proteasome system enzymes implicated in neuronal function
| Protein | Neuronal function | Substrates | References |
|---|---|---|---|
| Ubiquitin-conjugating (E2) enzymes | |||
| E2-25K/Hip-2 | Mediating amyloid-β neurotoxicity; control of aggregate formation and cell death in polyglutamine diseases | ? | Song et al. (2003), de Pril et al. (2007) |
| UbcD1 | Dendritic pruning in Drosophila through caspase regulation | DIAP1 | Kuo et al. (2006) |
| Ubiquitin and polyubiquitin ligase (E3/E4) enzymes | |||
| Ube3a/E6-AP | Loss of function of maternal copy leads to Angelman’s syndrome, defects in hippocampal LTP, decreases in dendritic spine density, experience-dependent maturation of neocortex | Arc/Arg3.1 | Dindot et al. (2008), Greer et al. (2010), Jiang et al. (1998), Kishino et al. (1997), Lu et al. (2009), Matsuura et al. (1997), Sato & Stryker (2010), Weeber et al. (2003), Yashiro et al. (2009) |
| F-box protein 40 | Copy number variations lead to autism susceptibility | ? | Glessner et al. (2009) |
| COP1 | Copy number variations lead to autism susceptibility | ? | Glessner et al. (2009) |
| APC/C | Axon growth, dendritic growth, synaptogenesis, L-LTP in mice, glutamate receptor trafficking and abundance in C. elegans, control of antioxidant status | Liprin-α Id1 Pfkfb3 | Burbea et al. (2002), Herrero-Mendez et al. (2009), Juo & Kaplan (2004), Kim et al. (2009), Konishi et al. (2004), Li et al. (2008), van Roessel et al. (2004) |
| highwire/RPM-1/Phr1 | Synapse formation at the Drosophila NMJ, glutamate receptor endocytosis in C. elegans | ? | Bloom et al. (2007), Burgess et al. (2004), DiAntonio et al. (2001), Liao et al. (2004), Nakata et al. (2005), Park et al. (2009), Schaefer et al. (2000), Wan et al. (2000), Wu et al. (2005), Zhen et al. (2000) |
| PDZRN3A | NMJ formation in mice | MuSK | Lu et al. (2007) |
| SKR-1 | Synapse elimination at HSNL synapses in C. elegans | ? | Ding et al. (2007) |
| SCFSEL-10 | Synapse elimination at HSNL synapses in C. elegans | ? | Ding et al. (2007) |
| SCFβTrCP/LIN-23 | Glutamate receptor abundance in C. elegans and regulation of PSD-associated protein SPAR | β-catenin SPAR | Ang et al. (2008), Dreier et al. (2005) |
| mindbomb1 | Neuronal branching | ? | Choe et al. (2007) |
| KEL-8 | Glutamate receptor abundance in C. elegans | ? | Schaefer & Rongo (2006) |
| SCFFSN-10 | Synapse development and glutamate receptor abundance in C. elegans | ? | Liao et al. (2004), Park et al. (2009) |
| Mdm2 | AMPA receptor endocytosis | PSD-95 | Colledge et al. (2003) |
| SCFFbx2 | Regulation of NMDA receptor abundance | GluN1 | Kato et al. (2005), Nelson et al. (2006) |
| CHIP | Enhances parkin ubiquitin ligase activity, NMDA receptor abundance | GluN2A | Imai et al. (2002), Nelson et al. (2006) |
| mindbomb2 | NMDA receptor abundance | GluN2B | Jurd et al. (2008) |
| Cul3 | GluK2 abundance | GluK2 | Salinas et al. (2006) |
| Siah1A | mGluR abundance | mGluR1/5 | Ishikawa et al. (1999), Moriyoshi et al. (2004) |
| Parkin | Controls excitatory synapse number, protects against excitotoxic cell death, regulates ASICs. Copy number variations lead to autism susceptibility; mutations associated with Parkinson’s disease. | PICK1 α-synuclein | Cha et al. (2005), Darios et al. (2003), Glessner et al. (2009), Helton et al. (2008), Henn et al. (2007), Joch et al. (2007), Kitada et al. (1998), Ng et al. (2009), Palacino et al. (2004), Shimura et al. (2001), Staropoli et al. (2003) |
| TRIM3 | Controls dendritic spine size | GKAP | Hung et al. (2010) |
| RNF182 | Brain enriched and upregulated in Alzheimer’s patient brains, regulates cell viability | ATP6V0C | Liu et al. (2008) |
| Mahogunin | Loss of function causes age-dependent neurodegeneration | ? | He et al. (2003), Phan et al. (2002) |
| UFD2 | Loss of function delays Wallerian degeneration | ? | Mack et al. (2001), Zhai et al. (2003) |
| Deubiquitinases | |||
| Ap-Uch/UCH-L3 | Working memory in Aplysia; working memory in mice | ? | Hegde et al. (1993), Wood et al. (2005) |
| fat facets | Synapse formation in Drosophila eye and NMJ; presynaptic membrane dynamics | Epsin 1 | Cadavid et al. (2000), Chen et al. (2003), DiAntonio et al. (2001), Huang et al. (1995), Wan et al. (2000) |
| Usp14 | Muscle mass development and control of motor endplate size, behavioral defects, and increased IPSCs in the ataxia mutant mouse | GABAAR? | Anderson et al. (2005), Chen et al. (2009), Lappe-Siefke et al. (2009), Walters et al. (2008), Wilson et al. (2002) |
| UCH-L1 | Associated with early-onset familial Parkinson’s disease; control of spine size, density, and synapse number; synaptic transmission at the NMJ | ? | Cartier et al. (2009), Chen et al. (2010), Leroy et al. (1998), Saigoh et al. (1999) |
| UBP2 | Overexpression delays Wallerian degeneration | ? | Zhai et al. (2003) |
| Ataxin-3 | Mutated in Machado-Joseph disease | ? | Kawaguchi et al. (1994) |
?, unknown; DIAP1, Drosophila inhibitor of apoptosis; LTP, long-term potentiation; Pfkfb3, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, isoform 3; NMJ, neuromuscular junction; HSNL, hermaphrodite-specific motor neuron; PSD, postsynaptic density; ASIC, acid-sensing ion channel; IPSC, inhibitory postsynaptic current.