PMID- 28158493
OWN - NLM
STAT- MEDLINE
DCOM- 20190626
LR  - 20201021
IS  - 1460-2199 (Electronic)
IS  - 1047-3211 (Linking)
VI  - 28
IP  - 4
DP  - 2018 Apr 1
TI  - Regulation of Dendritic Spine Morphology in Hippocampal Neurons by Copine-6.
PG  - 1087-1104
LID - 10.1093/cercor/bhx009 [doi]
AB  - Dendritic spines compartmentalize information in the brain, and their 
      morphological characteristics are thought to underly synaptic plasticity. Here we 
      identify copine-6 as a novel modulator of dendritic spine morphology. We found 
      that brain-derived neurotrophic factor (BDNF) - a molecule essential for 
      long-term potentiation of synaptic strength - upregulated and recruited copine-6 
      to dendritic spines in hippocampal neurons. Overexpression of copine-6 increased 
      mushroom spine number and decreased filopodia number, while copine-6 knockdown 
      had the opposite effect and dramatically increased the number of filopodia, which 
      lacked PSD95. Functionally, manipulation of post-synaptic copine-6 levels 
      affected miniature excitatory post-synaptic current (mEPSC) kinetics and evoked 
      synaptic vesicle recycling in contacting boutons, and post-synaptic knockdown of 
      copine-6 reduced hippocampal LTP and increased LTD. Mechanistically, copine-6 
      promotes BDNF-TrkB signaling and recycling of activated TrkB receptors back to 
      the plasma membrane surface, and is necessary for BDNF-induced increases in 
      mushroom spines in hippocampal neurons. Thus copine-6 regulates BDNF-dependent 
      changes in dendritic spine morphology to promote synaptic plasticity.
FAU - Burk, Katja
AU  - Burk K
AD  - Trans-synaptic Signaling Group, European Neuroscience Institute, Grisebachstrasse 
      5, 37077 Gottingen, Germany.
FAU - Ramachandran, Binu
AU  - Ramachandran B
AD  - Trans-synaptic Signaling Group, European Neuroscience Institute, Grisebachstrasse 
      5, 37077 Gottingen, Germany.
FAU - Ahmed, Saheeb
AU  - Ahmed S
AD  - Trans-synaptic Signaling Group, European Neuroscience Institute, Grisebachstrasse 
      5, 37077 Gottingen, Germany.
AD  - Department of Diagnostic and Interventional Radiology, University Medical Center 
      Gottingen, Robert Koch Strasse 40, 37075 Gottingen, Germany.
FAU - Hurtado-Zavala, Joaquin I
AU  - Hurtado-Zavala JI
AD  - Trans-synaptic Signaling Group, European Neuroscience Institute, Grisebachstrasse 
      5, 37077 Gottingen, Germany.
FAU - Awasthi, Ankit
AU  - Awasthi A
AD  - Trans-synaptic Signaling Group, European Neuroscience Institute, Grisebachstrasse 
      5, 37077 Gottingen, Germany.
FAU - Benito, Eva
AU  - Benito E
AD  - German Center for Neurodegenerative Diseases (DZNE) Gottingen, von Siebold Str. 
      3A, 37075 Gottingen , Germany.
FAU - Faram, Ruth
AU  - Faram R
AD  - MRC Anatomical Neuropharmacology Unit, University of Oxford, Mansfield Road, 
      Oxford OX1 3TH , UK.
FAU - Ahmad, Hamid
AU  - Ahmad H
AD  - Trans-synaptic Signaling Group, European Neuroscience Institute, Grisebachstrasse 
      5, 37077 Gottingen, Germany.
AD  - Johannes Gutenberg University Mainz, Saarstrasse 21, 55122 Mainz, Germany.
FAU - Swaminathan, Aarti
AU  - Swaminathan A
AD  - Trans-synaptic Signaling Group, European Neuroscience Institute, Grisebachstrasse 
      5, 37077 Gottingen, Germany.
FAU - McIlhinney, Jeffrey
AU  - McIlhinney J
AD  - MRC Anatomical Neuropharmacology Unit, University of Oxford, Mansfield Road, 
      Oxford OX1 3TH , UK.
FAU - Fischer, Andre
AU  - Fischer A
AD  - German Center for Neurodegenerative Diseases (DZNE) Gottingen, von Siebold Str. 
      3A, 37075 Gottingen , Germany.
FAU - Perestenko, Pavel
AU  - Perestenko P
AD  - MRC Anatomical Neuropharmacology Unit, University of Oxford, Mansfield Road, 
      Oxford OX1 3TH , UK.
FAU - Dean, Camin
AU  - Dean C
AD  - Trans-synaptic Signaling Group, European Neuroscience Institute, Grisebachstrasse 
      5, 37077 Gottingen, Germany.
LA  - eng
GR  - Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cereb Cortex
JT  - Cerebral cortex (New York, N.Y. : 1991)
JID - 9110718
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (CPNE6 protein, rat)
RN  - 0 (Carrier Proteins)
RN  - 0 (Disks Large Homolog 4 Protein)
RN  - 0 (MAP2 protein, rat)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Slc32a1 protein, rat)
RN  - 0 (Vesicular Glutamate Transport Protein 1)
RN  - 0 (Vesicular Inhibitory Amino Acid Transport Proteins)
RN  - EC 2.7.10.1 (Ntrk2 protein, rat)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/pharmacology
MH  - Carrier Proteins/genetics/*metabolism
MH  - Cells, Cultured
MH  - Dendritic Spines/*physiology/ultrastructure
MH  - Disks Large Homolog 4 Protein/metabolism
MH  - Hippocampus/*cytology
MH  - Humans
MH  - Mice
MH  - Microtubule-Associated Proteins/metabolism
MH  - Nerve Tissue Proteins/genetics/*metabolism
MH  - Neurons/*physiology/*ultrastructure
MH  - Organ Culture Techniques
MH  - Rats
MH  - Receptor, trkB/genetics/metabolism
MH  - Synapses/drug effects/physiology/ultrastructure
MH  - Synaptic Potentials/drug effects/genetics
MH  - Synaptic Vesicles/drug effects/*physiology
MH  - Synaptosomes/metabolism/ultrastructure
MH  - Vesicular Glutamate Transport Protein 1/metabolism
MH  - Vesicular Inhibitory Amino Acid Transport Proteins/metabolism
EDAT- 2017/02/06 06:00
MHDA- 2019/06/27 06:00
CRDT- 2017/02/04 06:00
PHST- 2015/08/13 00:00 [received]
PHST- 2017/02/06 06:00 [pubmed]
PHST- 2019/06/27 06:00 [medline]
PHST- 2017/02/04 06:00 [entrez]
AID - 2967357 [pii]
AID - 10.1093/cercor/bhx009 [doi]
PST - ppublish
SO  - Cereb Cortex. 2018 Apr 1;28(4):1087-1104. doi: 10.1093/cercor/bhx009.