Abstract
Homeostatic scaling allows neurons to alter synaptic transmission to compensate for changes in network activity. Here, we show that suppression of network activity with tetrodotoxin, which increases surface expression of AMPA receptors (AMPARs), dramatically reduces levels of the deSUMOylating (where SUMO is small ubiquitin-like modifier) enzyme SENP1, leading to a consequent increase in protein SUMOylation. Overexpression of the catalytic domain of SENP1 prevents this scaling effect, and we identify Arc as a SUMO substrate involved in the tetrodotoxin-induced increase in AMPAR surface expression. Thus, protein SUMOylation plays an important and previously unsuspected role in synaptic trafficking of AMPARs that underlies homeostatic scaling.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cysteine Endopeptidases
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Cytoskeletal Proteins / metabolism
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Endopeptidases / genetics
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Endopeptidases / metabolism*
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / physiology
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HEK293 Cells
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Hippocampus / cytology
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Hippocampus / physiology*
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Homeostasis / physiology*
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Humans
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Nerve Tissue Proteins / metabolism
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Neuronal Plasticity / physiology
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Neurons / physiology*
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Organ Culture Techniques
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Protein Transport / physiology
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Rats
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Receptors, AMPA / metabolism
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Sodium Channel Blockers / pharmacology
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Sumoylation / drug effects
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Sumoylation / physiology*
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Synapses / metabolism*
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Tetrodotoxin / pharmacology
Substances
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Cytoskeletal Proteins
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Nerve Tissue Proteins
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Receptors, AMPA
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Sodium Channel Blockers
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activity regulated cytoskeletal-associated protein
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Tetrodotoxin
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Endopeptidases
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Cysteine Endopeptidases
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SENP1 protein, rat
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glutamate receptor ionotropic, AMPA 2
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glutamate receptor ionotropic, AMPA 1