Receptor trafficking and the regulation of synaptic plasticity by SUMO.
Timely and efficient information transfer at synapses is fundamental to brain function. Synapses are highly dynamic structures that exhibit long-lasting activity-dependent alterations to their structure and transmission efficiency, a phenomenon termed synaptic plasticity. These changes, which occur through alterations in presynaptic release or in the trafficking of postsynaptic receptor proteins, underpin the formation and stabilisation of neural circuits during brain development, and encode, process and store information essential for learning, memory and cognition. In recent years, it has emerged that the ubiquitin-like posttranslational modification SUMOylation is an important mediator of several aspects of neuronal and synaptic function. Through orchestrating synapse formation, presynaptic release and the trafficking of postsynaptic receptor proteins during forms of synaptic plasticity such as long-term potentiation, long-term depression and homeostatic scaling, SUMOylation is being increasingly appreciated to play a central role in neurotransmission. In this review, we outline key discoveries in this relatively new field, provide an update on recent progress regarding the targets and consequences of protein SUMOylation in synaptic function and plasticity, and highlight key outstanding questions regarding the roles of protein SUMOylation in the brain.
School of Biochemistry, Medical Sciences Building, University of Bristol, University Walk, Bristol, BS8 1TD, UK.
Jia
J
Luo
Emi
E
Ashikaga
Philip P
PP
Rubin
Michaela J
MJ
Heimann
Keri L
KL
Hildick
Paul
P
Bishop
Fatima
F
Girach
Fernando
F
Josa-Prado
Leo T H
LT
Tang
Ruth E
RE
Carmichael
Jeremy M
JM
Henley
Kevin A
KA
Wilkinson
D000818:Animals; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology; D000071679:Glycogen Synthase Kinase 3 beta; D051528:Guanylate Kinases / Q000502:physiology; D006801:Humans; D064326:MEF2 Transcription Factors / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology*; D055495:Neurogenesis; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000502:physiology; D015221:Potassium Channels / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology*; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000502:physiology; D025841:Small Ubiquitin-Related Modifier Proteins / Q000502:physiology*; D058207:Sumoylation / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D043743:Ubiquitin-Protein Ligase Complexes / Q000502:physiology
D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D051528:Guanylate Kinases; D064326:MEF2 Transcription Factors; D009419:Nerve Tissue Proteins; D051059:PTEN Phosphohydrolase; D015221:Potassium Channels; D043884:Receptor, Cannabinoid, CB1; D018092:Kainic Acid Receptors; D018094:Receptors, Metabotropic Glutamate; D017981:Receptors, Neurotransmitter; D017661:Receptors, Presynaptic; D025841:Small Ubiquitin-Related Modifier Proteins; D043743:Ubiquitin-Protein Ligase Complexes; C106868:CASK kinases