title: Homeostatic synaptic scaling is regulated by protein SUMOylation.
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.
authors.affiliation: Medical Research Council Centre for Synaptic Plasticity, School of Biochemistry, University of Bristol, Bristol BS8 1TD, United Kingdom.
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Craig
authors.forename: Nadia
authors.initials: N
authors.lastname: Jaafari
authors.forename: Milos M
authors.initials: MM
authors.lastname: Petrovic
authors.forename: Susan C
authors.initials: SC
authors.lastname: Jacobs
authors.forename: Philip P
authors.initials: PP
authors.lastname: Rubin
authors.forename: Jack R
authors.initials: JR
authors.lastname: Mellor
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Henley
mesh_terms: D000818:Animals; D003546:Cysteine Endopeptidases; D003598:Cytoskeletal Proteins / Q000378:metabolism; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009924:Organ Culture Techniques; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D058207:Sumoylation / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D003546:Cysteine Endopeptidases; D003598:Cytoskeletal Proteins; D010450:Endopeptidases; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; C092069:activity regulated cytoskeletal-associated protein; C000630128:SENP1 protein, rat; C104722:glutamate receptor ionotropic, AMPA 2