Drebrin A regulates dendritic spine plasticity and synaptic function in mature cultured hippocampal neurons.
Drebrin A, one of the most abundant neuron-specific F-actin-binding proteins, is found exclusively in dendrites and is particularly concentrated in dendritic spines receiving excitatory inputs. We investigated the role of drebrin A in synaptic transmission and found that overexpression of drebrin A augmented the glutamatergic synaptic transmission, probably through an increase of active synaptic site density. Interestingly, overexpression of drebrin A also affected the frequency, amplitude and kinetics of miniature inhibitory postsynaptic currents (mIPSCs), despite the fact that GABAergic synapse density and transmission efficacy were not modified. Downregulation of drebrin A led to a decrease of both glutamatergic and GABAergic synaptic activity. In heterologous cells, drebrin A reorganized and stabilized F-actin and these effects were mediated by its actin-binding domain. Thus, drebrin A might regulate dendritic spine morphology via regulation of actin cytoskeleton remodeling and dynamics. Our data demonstrate for the first time that drebrin A modulates glutamatergic and GABAergic synaptic activities.
Ivanov
Anton
A
INMED/INSERM U29, Parc Scientifique de Luminy, 13273, Marseille, France.
Esclapez
Monique
M
Pellegrino
Christophe
C
Shirao
Tomoaki
T
Ferhat
Lotfi
L
D000199:Actins / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D003599:Cytoskeleton / Q000378:metabolism; D004274:DNA, Recombinant / Q000096:biosynthesis*; D049229:Dendritic Spines / Q000378:metabolism* / Q000648:ultrastructure; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000166:cytology; D053444:Inhibitory Postsynaptic Potentials; D018613:Microscopy, Confocal; D009473:Neuronal Plasticity; D009479:Neuropeptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs / Q000502:physiology; D051381:Rats; D018091:Receptors, AMPA / Q000737:chemistry / Q000378:metabolism; D011963:Receptors, GABA-A / Q000737:chemistry / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D009435:Synaptic Transmission
D000199:Actins; D004274:DNA, Recombinant; D009479:Neuropeptides; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D011993:Recombinant Fusion Proteins; C053386:drebrins; D049452:Green Fluorescent Proteins