Synaptic activity controls dendritic spine morphology by modulating eEF2-dependent BDNF synthesis.
Activity-dependent changes in synaptic structure and spine morphology are required for learning and memory, and depend on protein translation. We show that the kinase for eukaryotic elongation factor 2 (eEF2K) regulates dendritic spine stability and synaptic structure by modulating activity-dependent dendritic BDNF synthesis. Specifically RNAi knockdown of eEF2K reduces dendritic spine stability and inhibits dendritic BDNF protein expression; whereas overexpression of a constitutively activated eEF2K induces spine maturation and increases expression of dendritic BDNF. Furthermore, BDNF overexpression rescues the spine stability reduced by RNAi knockdown of eEF2K. We also show that synaptic activity-dependent spine maturation and dendritic BDNF protein expression depend on mGluR/EF2K-induced eEF2 phosphorylation. We propose that the eEF2K/eEF2 pathway is a key biochemical sensor that couple neuronal activity to spine plasticity, by controlling the dendritic translation of BDNF.
Verpelli
Chiara
C
Consiglio Nazionale delle Ricerche Neuroscience Institute, Milan, Italy.
Piccoli
Giovanni
G
Zibetti
Cristina
C
Zanchi
Alice
A
Gardoni
Fabrizio
F
Huang
Kun
K
Brambilla
Dario
D
Di Luca
Monica
M
Battaglioli
Elena
E
Sala
Carlo
C
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000201:enzymology / Q000502:physiology*; D054736:Elongation Factor 2 Kinase / Q000235:genetics / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D009474:Neurons / Q000502:physiology; D020652:Peptide Elongation Factor 2 / Q000378:metabolism*; D010766:Phosphorylation; D034622:RNA Interference; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D015398:Signal Transduction; D013569:Synapses / Q000201:enzymology / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D020652:Peptide Elongation Factor 2; D018094:Receptors, Metabotropic Glutamate; D054736:Elongation Factor 2 Kinase