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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.

SUBMITTER: Craig TJ

PROVIDER: S-EPMC3391081 | biostudies-other | 2012 Jun

REPOSITORIES: biostudies-other

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Homeostatic synaptic scaling is regulated by protein SUMOylation.

Craig Tim J TJ Jaafari Nadia N Petrovic Milos M MM Jacobs Susan C SC Rubin Philip P PP Mellor Jack R JR Henley Jeremy M JM

The Journal of biological chemistry 20120511 27

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 ide ...[more]

PMID: 22582390

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