Activity-Induced SUMOylation of Neuronal Nitric Oxide Synthase Is Associated with Plasticity of Synaptic Transmission and Extracellular Signal-Regulated Kinase 1/2 Signaling.
Antioxid Redox Signal
; 32(1): 18-34, 2020 01 01.
Article
in En
| MEDLINE
| ID: mdl-31642335
ABSTRACT
Aims:
Neuronal nitric oxide synthase (nNOS) and nitric oxide (NO) signaling have been implicated in learning, memory, and underlying long-lasting synaptic plasticity. In this study, we aimed at detecting whether nNOS is a target protein of SUMOylation in the hippocampus and its contributions to hippocampal long-term potentiation (LTP) of synaptic transmission.Results:
We showed that N-methyl-d-aspartate receptor-dependent neuronal activity enhancement induced the attachment of small ubiquitin-like modifier 1 (SUMO1) to nNOS. Protein inhibitor of activated STAT3 (PIAS3) promoted SUMO1 conjugation at K725 and K739 on nNOS, which upregulated NO production and nNOS S1412 phosphorylation (activation). In addition, the N-terminus (amino acids 43-86) of PIAS3 bound nNOS directly. Tat-tagged PIAS3 segment representing amino acids 43-86, a cell-permeable peptide containing PIAS3 residues 43-86, suppressed activity-induced nNOS SUMOylation by disrupting PIAS3-nNOS association. It also decreased LTP-related expression of Arc and brain-derived neurotrophic factor and blocked signaling via extracellular signal-regulated kinase (ERK) 1/2 and Elk-1 in the hippocampus. More importantly, PIAS3-mediated nNOS SUMOylation was required for activity-regulated ERK1/2 activation in nNOS-positive neurons and hippocampal LTP induction. Innovation andConclusion:
These findings indicated that network activity-regulated nNOS SUMOylation underlies excitatory synaptic LTP by facilitating nNOS-NO-ERK1/2 signal cascades.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Molecular Chaperones
/
SUMO-1 Protein
/
Nitric Oxide Synthase Type I
/
Protein Inhibitors of Activated STAT
/
Hippocampus
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
Antioxid Redox Signal
Journal subject:
METABOLISMO
Year:
2020
Document type:
Article
Affiliation country: