Drebrin A is one of the most abundant neuron-specific
binding proteins of
F-actin and its expression is increased in parallel with synapse formation.
Drebrin A is particularly concentrated in dendritic spines, postsynaptic sides of excitatory glutamatergic synapses. More recently, Ferhat and colleagues reported the functional role of
drebrin A in regulating synaptic transmission. Indeed, our study showed that overexpression of
drebrin A induced an increase of glutamatergic but not GABAergic synapses and resulted in the alteration of the normal excitatory-inhibitory ratio in favor of excitation in mature hippocampal neurons. Downregulation of
drebrin A expression by
antisense oligonucleotides resulted in the decrease of both miniature- glutamatergic and GABAergic synaptic activities without affecting the excitatory-inhibitory ratio. Studies performed in heterologous cells revealed that
drebrin A reorganized the actin filaments and stabilized them and that these effects are depend upon its actin-binding domain. These results suggest that
drebrin A regulates dendritic spine morphology, size and density, presumably via regulation of actin cytoskeleton remodeling and dynamics. These data demonstrate for the first time that an
actin-binding protein such as
drebrin A regulates both glutamatergic and GABAergic synaptic transmissions, probably through an increase of active synaptic site density for glutamatergic transmission and through homeostatic mechanisms for the GABAergic one.It is appealing to suggest that abnormalities in the expression of
drebrin A may result in aberrant synapse development and/or loss of synapses leading to synaptic dysfunction, which underlies
cognitive impairment accompanying
neurological disorders such as
Alzheimer's disease,
Down syndrome as well as normal aging.