Regulation of Dendritic Spine Morphology in Hippocampal Neurons by Copine-6.
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.
Trans-synaptic Signaling Group, European Neuroscience Institute, Grisebachstrasse 5, 37077 Göttingen, Germany.
Katja
K
Burk
Trans-synaptic Signaling Group, European Neuroscience Institute, Grisebachstrasse 5, 37077 Göttingen, Germany.
Binu
B
Ramachandran
Trans-synaptic Signaling Group, European Neuroscience Institute, Grisebachstrasse 5, 37077 Göttingen, Germany.|Department of Diagnostic and Interventional Radiology, University Medical Center Göttingen, Robert Koch Strasse 40, 37075 Göttingen, Germany.
Saheeb
S
Ahmed
Trans-synaptic Signaling Group, European Neuroscience Institute, Grisebachstrasse 5, 37077 Göttingen, Germany.
Joaquin I
JI
Hurtado-Zavala
Trans-synaptic Signaling Group, European Neuroscience Institute, Grisebachstrasse 5, 37077 Göttingen, Germany.
Ankit
A
Awasthi
German Center for Neurodegenerative Diseases (DZNE) Göttingen, von Siebold Str. 3A, 37075 Göttingen , Germany.
Eva
E
Benito
MRC Anatomical Neuropharmacology Unit, University of Oxford, Mansfield Road, Oxford OX1 3TH , UK.
Ruth
R
Faram
Trans-synaptic Signaling Group, European Neuroscience Institute, Grisebachstrasse 5, 37077 Göttingen, Germany.|Johannes Gutenberg University Mainz, Saarstrasse 21, 55122 Mainz, Germany.
Hamid
H
Ahmad
Trans-synaptic Signaling Group, European Neuroscience Institute, Grisebachstrasse 5, 37077 Göttingen, Germany.
Aarti
A
Swaminathan
MRC Anatomical Neuropharmacology Unit, University of Oxford, Mansfield Road, Oxford OX1 3TH , UK.
Jeffrey
J
McIlhinney
German Center for Neurodegenerative Diseases (DZNE) Göttingen, von Siebold Str. 3A, 37075 Göttingen , Germany.
Andre
A
Fischer
MRC Anatomical Neuropharmacology Unit, University of Oxford, Mansfield Road, Oxford OX1 3TH , UK.
Pavel
P
Perestenko
Trans-synaptic Signaling Group, European Neuroscience Institute, Grisebachstrasse 5, 37077 Göttingen, Germany.
Camin
C
Dean
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000502:physiology* / Q000648:ultrastructure; D000076122:Disks Large Homolog 4 Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure*; D009924:Organ Culture Techniques; D051381:Rats; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D055366:Synaptic Potentials / Q000187:drug effects / Q000235:genetics; D013572:Synaptic Vesicles / Q000187:drug effects / Q000502:physiology*; D013574:Synaptosomes / Q000378:metabolism / Q000648:ultrastructure; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; C000616617:CPNE6 protein, rat; D002352:Carrier Proteins; D000076122:Disks Large Homolog 4 Protein; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C118623:Slc32a1 protein, rat; D050598:Vesicular Glutamate Transport Protein 1; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C000621230:Ntrk2 protein, rat; D020813:Receptor, trkB