PMID- 28670266
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1662-5099 (Print)
IS  - 1662-5099 (Electronic)
IS  - 1662-5099 (Linking)
VI  - 10
DP  - 2017
TI  - GSK3alpha and GSK3beta Phosphorylate Arc and Regulate its Degradation.
PG  - 192
LID - 10.3389/fnmol.2017.00192 [doi]
LID - 192
AB  - The selective and neuronal activity-dependent degradation of synaptic proteins 
      appears to be crucial for long-term synaptic plasticity. One such protein is 
      activity-regulated cytoskeleton-associated protein (Arc), which regulates the 
      synaptic content of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 
      receptors (AMPAR), excitatory synapse strength and dendritic spine morphology. 
      The levels of Arc protein are tightly regulated, and its removal occurs via 
      proteasome-mediated degradation that requires prior ubiquitination. Glycogen 
      synthase kinases alpha and beta (GSK3alpha, GSKbeta; collectively named GSK3alpha/beta) are 
      serine-threonine kinases with abundant expression in the central nervous system. 
      Both GSK3 isozymes are tonically active under basal conditions, but their 
      activity is regulated by intra- and extracellular factors, intimately involved in 
      neuronal activity. Similar to Arc, GSK3alpha and GSK3beta contribute to synaptic 
      plasticity and the structural plasticity of dendritic spines. The present study 
      identified Arc as a GSK3alpha/beta substrate and showed that GSKbeta promotes Arc 
      degradation under conditions that induce de novo Arc synthesis. We also found 
      that GSK3alpha/beta inhibition potentiated spine head thinning that was caused by the 
      prolonged stimulation of N-methyl-D-aspartate receptors (NMDAR). Furthermore, 
      overexpression of Arc mutants that were resistant to GSK3beta-mediated 
      phosphorylation or ubiquitination resulted in a stronger reduction of dendritic 
      spine width than wildtype Arc overexpression. Thus, GSK3beta terminates Arc 
      expression and limits its effect on dendritic spine morphology. Taken together, 
      the results identify GSK3alpha/beta-catalyzed Arc phosphorylation and degradation as a 
      novel mechanism for controlling the duration of Arc expression and function.
FAU - Gozdz, Agata
AU  - Gozdz A
AD  - Laboratory of Molecular and Cellular Neurobiology, International Institute of 
      Molecular and Cell BiologyWarsaw, Poland.
FAU - Nikolaienko, Oleksii
AU  - Nikolaienko O
AD  - Department of Biomedicine and KG Jebsen Centre for Research on Neuropsychiatric 
      Disorders, University of BergenBergen, Norway.
FAU - Urbanska, Malgorzata
AU  - Urbanska M
AD  - Laboratory of Molecular and Cellular Neurobiology, International Institute of 
      Molecular and Cell BiologyWarsaw, Poland.
AD  - Department of Neurology and Epileptology, Children's Memorial Health 
      InstituteWarsaw, Poland.
FAU - Cymerman, Iwona A
AU  - Cymerman IA
AD  - Laboratory of Molecular and Cellular Neurobiology, International Institute of 
      Molecular and Cell BiologyWarsaw, Poland.
FAU - Sitkiewicz, Ewa
AU  - Sitkiewicz E
AD  - Institute of Biochemistry and Biophysics, Polish Academy of ScienceWarsaw, 
      Poland.
FAU - Blazejczyk, Magdalena
AU  - Blazejczyk M
AD  - Laboratory of Molecular and Cellular Neurobiology, International Institute of 
      Molecular and Cell BiologyWarsaw, Poland.
FAU - Dadlez, Michal
AU  - Dadlez M
AD  - Institute of Biochemistry and Biophysics, Polish Academy of ScienceWarsaw, 
      Poland.
FAU - Bramham, Clive R
AU  - Bramham CR
AD  - Department of Biomedicine and KG Jebsen Centre for Research on Neuropsychiatric 
      Disorders, University of BergenBergen, Norway.
FAU - Jaworski, Jacek
AU  - Jaworski J
AD  - Laboratory of Molecular and Cellular Neurobiology, International Institute of 
      Molecular and Cell BiologyWarsaw, Poland.
LA  - eng
PT  - Journal Article
DEP - 20170616
PL  - Switzerland
TA  - Front Mol Neurosci
JT  - Frontiers in molecular neuroscience
JID - 101477914
PMC - PMC5472658
OTO - NOTNLM
OT  - Arc/Arg3.1
OT  - GSK3
OT  - NMDA
OT  - dendritic spines
OT  - neuronal activity
OT  - phosphorylation
OT  - proteasomal degradation
EDAT- 2017/07/04 06:00
MHDA- 2017/07/04 06:01
PMCR- 2017/01/01
CRDT- 2017/07/04 06:00
PHST- 2017/02/24 00:00 [received]
PHST- 2017/05/30 00:00 [accepted]
PHST- 2017/07/04 06:00 [entrez]
PHST- 2017/07/04 06:00 [pubmed]
PHST- 2017/07/04 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.3389/fnmol.2017.00192 [doi]
PST - epublish
SO  - Front Mol Neurosci. 2017 Jun 16;10:192. doi: 10.3389/fnmol.2017.00192. 
      eCollection 2017.