Activity-dependent SUMOylation of the brain-specific scaffolding protein GISP

Kantamneni, Sriharsha; Wilkinson, Kevin A.; Jaafari, Nadia; Ashikaga, Emi; Rocca, Daniel L.; Rubin, Philip; Jacobs, Sydney; Nishimune, Atsushi; Henley, Jeremy M.

doi:10.1016/j.bbrc.2011.05.060

Cited by 18 publications

(23 citation statements)

References 21 publications

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“…We, and others have also identified other synaptic SUMO substrates e.g. [12], [13] and SUMOylation has been implicated in several clinically important neurological and neurodegenerative diseases [14]. Interestingly, although there is currently no evidence to suggest that AMPARs are direct targets of SUMOylation [8], we have recently demonstrated that SUMOylation can regulate AMPAR trafficking during homeostatic synaptic plasticity [13].…”

Section: Introductionmentioning

confidence: 79%

SUMOylation Is Required for Glycine-Induced Increases in AMPA Receptor Surface Expression (ChemLTP) in Hippocampal Neurons

et al. 2013

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Multiple pathways participate in the AMPA receptor trafficking that underlies long-term potentiation (LTP) of synaptic transmission. Here we demonstrate that protein SUMOylation is required for insertion of the GluA1 AMPAR subunit following transient glycine-evoked increase in AMPA receptor surface expression (ChemLTP) in dispersed neuronal cultures. ChemLTP increases co-localisation of SUMO-1 and the SUMO conjugating enzyme Ubc9 and with PSD95 consistent with the recruitment of SUMOylated proteins to dendritic spines. In addition, we show that ChemLTP increases dendritic levels of SUMO-1 and Ubc9 mRNA. Consistent with activity dependent translocation of these mRNAs to sites near synapses, levels of the mRNA binding and dendritic transport protein CPEB are also increased by ChemLTP. Importantly, reducing the extent of substrate protein SUMOylation by overexpressing the deSUMOylating enzyme SENP-1 or inhibiting SUMOylation by expressing dominant negative Ubc9 prevent the ChemLTP-induced increase in both AMPAR surface expression and dendritic SUMO-1 mRNA. Taken together these data demonstrate that SUMOylation of synaptic protein(s) involved in AMPA receptor trafficking is necessary for activity-dependent increases in AMPAR surface expression.

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Section: Introductionmentioning

confidence: 79%

SUMOylation Is Required for Glycine-Induced Increases in AMPA Receptor Surface Expression (ChemLTP) in Hippocampal Neurons

et al. 2013

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“…However, SUMOylation appears to play a much more pervasive regulatory role in cells; recent studies have shown SUMOylation of ion channels, membrane-bound receptors, solute carriers, and mitochondrial or neuronal scaffolding and signaling proteins (4)(5)(6), leading to the notion that SUMOylation is a core regulatory process in all cellular subcompartments. This triggered substantial activities to develop tools for the discovery and validation of SUMOylation substrates in cells, which has proven difficult.…”

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confidence: 99%

In vivo localization and identification of SUMOylated proteins in the brain of His ₆ -HA-SUMO1 knock-in mice

Tirard

Hsiao

Nikolov

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

125

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SUMOylation, an essential posttranslational protein modification, is involved in many eukaryotic cellular signaling pathways. The identification of SUMOylated proteins is difficult, because SUMOylation sites in proteins are hard to predict, SUMOylated protein states are transient in vivo and labile in vitro, only a small substrate fraction is SUMOylated in vivo, and identification tools for natively SUMOylated proteins are rare. To solve these problems, we generated knock-in mice expressing His 6 -HA-SUMO1. By anti-HA immunostaining, we show that SUMO1 conjugates in neurons are only detectable in nuclei and annulate lamellae. By anti-HA affinity purification, we identified several hundred candidate SUMO1 substrates, of which we validated Smchd1, Ctip2, TIF1γ, and Zbtb20 as novel substrates. The knock-in mouse represents an excellent mammalian model for studies on SUMO1 localization and screens for SUMO1 conjugates in vivo.synapse | affinity purification S UMOylation is a conserved posttranslational protein modification in eukaryotes, akin to ubiquitylation, and can affect the localization, interactions, function, or stability of substrates (1). SUMOylation processes participate in many cellular signaling pathways, where they intersect with other posttranslational regulatory processes such as phosphorylation, ubiquitylation, or acetylation. Consequently, many cellular processes, from nuclear transport to neuronal synaptic transmission, are controlled by SUMOylation (2), and key SUMOylation substrates or altered SUMOylation are involved in many diseases, from cancer to neurological disorders (3).Reflecting the prominent nuclear role of SUMOylation, most known SUMOylation substrates are nuclear proteins (1, 2). However, SUMOylation appears to play a much more pervasive regulatory role in cells; recent studies have shown SUMOylation of ion channels, membrane-bound receptors, solute carriers, and mitochondrial or neuronal scaffolding and signaling proteins (4-6), leading to the notion that SUMOylation is a core regulatory process in all cellular subcompartments. This triggered substantial activities to develop tools for the discovery and validation of SUMOylation substrates in cells, which has proven difficult.Mammalian genomes contain four SUMO genes, encoding SUMO1, SUMO2, SUMO3 (7, 8), and SUMO4, of which SUMO4 is poorly characterized (9). SUMO2 and SUMO3 are almost identical, whereas SUMO1 is 50% homologous to SUMO2 and SUMO3. The 3D structure of SUMOs is similar to that of ubiquitin (10), and like ubiquitylation, SUMOylation involves an E1 activating enzyme, E2 conjugating enzymes, and E3 ligases (1,2,7,8).SUMOs are conjugated to lysine residues, often within a ϕKxD/E motif (ϕ, hydrophobic residue; x, any amino acid) (1), but in general SUMO acceptor lysines cannot be predicted, which prevents the identification of SUMO substrates by bioinformatics (1). Further, SUMOylated states of proteins are transient in vivo and labile in vitro because of isopeptidases that revert SUMOylation (1), and usually only a small f...

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“…For example, SUMOylation can promote non-covalent interactions with proteins containing SUMO interacting motifs (SIMs), occlude binding sites, modulate protein localisation and/or regulate proteostasis [55]. In particular, SUMOylation is a key regulator of neuronal function [56], with numerous neuronal proteins shown to be targets for activity-dependent modification, including several involved in neurotransmission and plasticity such as the kainate-type glutamate receptor subunit GluK2 [57], the transcription factor CREB [58] and the postsynaptic density scaffold GISP [59].…”

Section: Sumoylationmentioning

confidence: 99%

Transcriptional and post-translational regulation of Arc in synaptic plasticity

Carmichael

Henley

2018

Seminars in Cell & Developmental Biology

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One of the most interesting features of Arc-dependent synaptic plasticity is how multiple types of synaptic activity can converge to alter Arc transcription and then diverge to induce different plasticity outcomes, ranging from AMPA receptor internalisation that promotes long-term depression (LTD), to actin stabilisation that promotes long-term potentiation (LTP). This diversity suggests that there must be numerous levels of control to ensure the temporal profile, abundance, localisation and function of Arc are appropriately regulated to effect learning and memory in the correct contexts. The activity-dependent transcription and post-translational modification of Arc are crucial regulators of synaptic plasticity, fine-tuning the function of this key protein depending on the specific situation. The extensive cross-talk between signalling pathways and the numerous routes of Arc regulation provide a complex interplay of processes in which Arc-mediated plasticity can be broadly induced, but specifically tailored to synaptic activity. Here we provide an overview what is currently known about these processes and potential future directions.

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Activity-dependent SUMOylation of the brain-specific scaffolding protein GISP

Cited by 18 publications

References 21 publications

SUMOylation Is Required for Glycine-Induced Increases in AMPA Receptor Surface Expression (ChemLTP) in Hippocampal Neurons

SUMOylation Is Required for Glycine-Induced Increases in AMPA Receptor Surface Expression (ChemLTP) in Hippocampal Neurons

In vivo localization and identification of SUMOylated proteins in the brain of His ₆ -HA-SUMO1 knock-in mice

Transcriptional and post-translational regulation of Arc in synaptic plasticity

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Activity-dependent SUMOylation of the brain-specific scaffolding protein GISP

Cited by 18 publications

References 21 publications

SUMOylation Is Required for Glycine-Induced Increases in AMPA Receptor Surface Expression (ChemLTP) in Hippocampal Neurons

SUMOylation Is Required for Glycine-Induced Increases in AMPA Receptor Surface Expression (ChemLTP) in Hippocampal Neurons

In vivo localization and identification of SUMOylated proteins in the brain of His 6 -HA-SUMO1 knock-in mice

Transcriptional and post-translational regulation of Arc in synaptic plasticity

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In vivo localization and identification of SUMOylated proteins in the brain of His ₆ -HA-SUMO1 knock-in mice