PMID- 28553222
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 1663-3563 (Print)
IS  - 1663-3563 (Electronic)
IS  - 1663-3563 (Linking)
VI  - 9
DP  - 2017
TI  - Dynamic Arc SUMOylation and Selective Interaction with F-Actin-Binding Protein 
      Drebrin A in LTP Consolidation In Vivo.
PG  - 8
LID - 10.3389/fnsyn.2017.00008 [doi]
LID - 8
AB  - Activity-regulatedcytoskeleton-associated protein (Arc) protein is implicated as 
      a master regulator of long-term forms of synaptic plasticity and memory 
      formation, but the mechanisms controlling Arc protein function are little known. 
      Post-translation modification by small ubiquitin-like modifier (SUMO) proteins 
      has emerged as a major mechanism for regulating protein-protein interactions and 
      function. We first show in cell lines that ectopically expressed Arc undergoes 
      mono-SUMOylation. The covalent addition of a single SUMO1 protein was confirmed 
      by in vitro SUMOylation of immunoprecipitated Arc. To explore regulation of 
      endogenous Arc during synaptic plasticity, we induced long-term potentiation 
      (LTP) in the dentate gyrus of live anesthetized rats. Using coimmunoprecipitation 
      of native proteins, we show that Arc synthesized during the maintenance phase of 
      LTP undergoes dynamic mono-SUMO1-ylation. Levels of unmodified Arc increase in 
      multiple subcellular fractions (cytosol, membrane, nuclear and cytoskeletal), 
      whereas enhanced Arc SUMOylation was specific to the synaptoneurosomal and the 
      cytoskeletal fractions. Dentate gyrus LTP consolidation requires a period of 
      sustained Arc synthesis driven by brain-derived neurotrophic factor (BDNF) 
      signaling. Local infusion of the BDNF scavenger, TrkB-Fc, during LTP maintenance 
      resulted in rapid reversion of LTP, inhibition of Arc synthesis and loss of 
      enhanced Arc SUMO1ylation. Furthermore, coimmunoprecipitation analysis showed 
      that SUMO1-ylated Arc forms a complex with the F-actin-binding protein drebrin A, 
      a major regulator of cytoskeletal dynamics in dendritic spines. Although Arc also 
      interacted with dynamin 2, calcium/calmodulindependentprotein kinase II-beta 
      (CaMKIIbeta), and postsynaptic density protein-95 (PSD-95), these complexes lacked 
      SUMOylated Arc. The results support a model in which newly synthesized Arc is 
      SUMOylated and targeted for actin cytoskeletal regulation during in vivo LTP.
FAU - Nair, Rajeevkumar R
AU  - Nair RR
AD  - Department of Biomedicine and KG Jebsen Centre for Neuropsychiatric Disorders, 
      University of BergenBergen, Norway.
FAU - Patil, Sudarshan
AU  - Patil S
AD  - Department of Biomedicine and KG Jebsen Centre for Neuropsychiatric Disorders, 
      University of BergenBergen, Norway.
FAU - Tiron, Adrian
AU  - Tiron A
AD  - Department of Biomedicine and KG Jebsen Centre for Neuropsychiatric Disorders, 
      University of BergenBergen, Norway.
FAU - Kanhema, Tambudzai
AU  - Kanhema T
AD  - Department of Biomedicine and KG Jebsen Centre for Neuropsychiatric Disorders, 
      University of BergenBergen, Norway.
FAU - Panja, Debabrata
AU  - Panja D
AD  - Department of Biomedicine and KG Jebsen Centre for Neuropsychiatric Disorders, 
      University of BergenBergen, Norway.
FAU - Schiro, Lars
AU  - Schiro L
AD  - Department of Biomedicine and KG Jebsen Centre for Neuropsychiatric Disorders, 
      University of BergenBergen, Norway.
FAU - Parobczak, Kamil
AU  - Parobczak K
AD  - Laboratory of Molecular and Systemic Neuromorphology, Department of 
      Neurophysiology, Nencki Institute of Experimental BiologyWarsaw, Poland.
FAU - Wilczynski, Grzegorz
AU  - Wilczynski G
AD  - Laboratory of Molecular and Systemic Neuromorphology, Department of 
      Neurophysiology, Nencki Institute of Experimental BiologyWarsaw, Poland.
FAU - Bramham, Clive R
AU  - Bramham CR
AD  - Department of Biomedicine and KG Jebsen Centre for Neuropsychiatric Disorders, 
      University of BergenBergen, Norway.
LA  - eng
PT  - Journal Article
DEP - 20170510
PL  - Switzerland
TA  - Front Synaptic Neurosci
JT  - Frontiers in synaptic neuroscience
JID - 101548972
PMC - PMC5426369
OTO - NOTNLM
OT  - actin cytoskeleton
OT  - brain-derived neurotrophic factor (BDNF)
OT  - dentate gyrus
OT  - hippocampus
OT  - immediate early protein
OT  - long-term potentiation (LTP)
OT  - small ubiquitin-like modifier (SUMO)
OT  - synaptic plasticity
EDAT- 2017/05/30 06:00
MHDA- 2017/05/30 06:01
PMCR- 2017/01/01
CRDT- 2017/05/30 06:00
PHST- 2016/12/08 00:00 [received]
PHST- 2017/04/21 00:00 [accepted]
PHST- 2017/05/30 06:00 [entrez]
PHST- 2017/05/30 06:00 [pubmed]
PHST- 2017/05/30 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.3389/fnsyn.2017.00008 [doi]
PST - epublish
SO  - Front Synaptic Neurosci. 2017 May 10;9:8. doi: 10.3389/fnsyn.2017.00008. 
      eCollection 2017.