Protein Sumoylation in Brain Development, Neuronal Morphology and Spinogenesis

Abstract

Small ubiquitin-like modifiers (SUMOs) are polypeptides resembling ubiquitin that are covalently attached to specific lysine residue of target proteins through a specific enzymatic pathway. Sumoylation is now seen as a key posttranslational modification involved in many biological processes, but little is known about how this highly dynamic protein modification is regulated in the brain. Disruption of the sumoylation enzymatic pathway during the embryonic development leads to lethality revealing a pivotal role for this protein modification during development. The main aim of this review is to briefly describe the SUMO pathway and give an overview of the sumoylation regulations occurring in brain development, neuronal morphology and synapse formation.

Comprehensive whole genome sequence analyses yields novel genetic and structural insights for Intellectual Disability

“…The candidate genes we identified converge onto the UPP, which is critically involved in neurodegenerative disease [45] and has important roles in neurodevelopmental disorders [45, 46]. This observation is consistent with the notion that they may be good candidates, and exemplifies the usefulness of probing molecular links among novel findings.…”

“…We investigated molecular links between our pathogenic and candidate genes; focused IPA and STRING pathway analyses revealed that all six connected to the ubiquitin proteasome degradation pathway (UPP) (Additional file 5: Figure S4) which has important roles in the structural development and function of the brain [45, 46]. We assessed the relative importance of this pathway and found the UPP was among significantly enriched pathways for PDS when compared with all KEGG pathway categories ( n  = 55) (Additional file 7: Table S5), in the UK10K patient cohort ( p  = 0.031), substantiating the importance of the UPP pathway in brain development.…”

Role of post-translational modifications on structure, function and pharmacology of class C G protein-coupled receptors

“…This PTM is not involved in degradation but rather stability (protection from ubiquitination), transcriptional regulation, cytosol-nuclear transport, and protein-protein interactions (Zhao, 2007). The attachment of these 11 kDa proteins has also been described as an important regulator of protein function in synaptic formation and brain development (Gwizdek et al, 2013). The group III metabotropic glutamate receptors have been suggested as targets for SUMOylation in in vitro studies on C-terminal domain constructs (Tang et al, 2005;Wilkinson et al, 2008).…”

mGlu5 receptors regulate synaptic sumoylation via a transient PKC-dependent diffusional trapping of Ubc9 into spines

“…These processes are almost always regulated by post-translational modifications such as phosphorylation or ubiquitination 1 . Sumoylation is emerging as a potent post-translational mechanism important for the regulation of synaptic transmission and plasticity [2][3][4] . The proper functioning of such modifications requires a rigorous spatial and temporal control of the associated enzymatic machinery.…”