Regulation of Neuronal Protein Trafficking and Translocation by SUMOylation

Abstract

Post-translational modifications of proteins are essential for cell function. Covalent modification by SUMO (small ubiquitin-like modifier) plays a role in multiple cell processes, including transcriptional regulation, DNA damage repair, protein localization and trafficking. Factors affecting protein localization and trafficking are particularly crucial in neurons because of their polarization, morphological complexity and functional specialization. SUMOylation has emerged as a major mediator of intranuclear and nucleo-cytoplasmic translocations of proteins involved in critical pathways such as circadian rhythm, apoptosis and protein degradation. In addition, SUMO-regulated re-localization of extranuclear proteins is required to sustain neuronal excitability and synaptic transmission. Thus, SUMOylation is a key arbiter of neuronal viability and function. Here, we provide an overview of recent advances in our understanding of regulation of neuronal protein localization and translocation by SUMO and highlight exciting areas of ongoing research.

Figure 1

Translocation of nuclear and nucleo-cytoplasmic proteins following SUMOylation. In the nucleus, SUMO modification leads to the formation of Cajal bodies, which are positive for coilin and SUMO. Other SUMO related nuclear structures are PML bodies, which contain SUMOylated PML and SUMOylated BMAL1. Caspases -2/-7/-8, GSK3beta and FAK translocate to the nucleus on SUMOylation. Abbreviations: PML: promyelocytic leukemia; BMAL: brain and muscle aryl hydrocarbon receptor nuclear translocator-like; GSK: glycogen synthase kinase; FAK: focal adhesion kinase.

Figure 2

Influence of SUMOylation on receptor trafficking and protein transport. (A) At the pre-synapse, de-SUMOylation of the cannabinoid receptor CB1 is proposed to lead to its internalization. In contrast, SUMOylation of group III mGluRs may lead to internalisation and/or degradation. Agonist-induced phosphorylation of GluK2 in post-synaptic kainate receptors causes endocytosis. Potential SUMO regulation of AMPA receptors may be via SUMO modified interacting proteins; (B) In the axon, the RNA binding protein La is SUMOylated, triggering its retrograde axonal transport through binding to dynein. Abbreviations: mGluR: metabotropic glutamate receptor.