Drebrin A plays a key role in cluster formation of F-actin and PSD-95 at postsynaptic site

Tomoaki Shirao

Abstract

Dendritic spines are the postsynaptic reception regions of most excitatory synapses, and spine formation is fundamental to the development of neuronal networks [1-3]. It has been reported that long thin protrusions from dendrites, dendritic filopodia, change into morphologically mature spines, such as mushroom-shaped or stubby spines. Previous studies suggested that the actin cytoskeleton mediated the morphology of both filopodia and spines. Drebrin A is a neuron-specific F-actin binding protein which is localized in dendritic spines. Immunocytochemical study showed that drebrin clustering in preceded PSD-95 clustering in dedritic filopodia. Suppression of drebrin A expression using antisense oligonucleotides inhibited the cluster formation of drebrin and PSD-95, and the spine formation. Replenishment of EGFP tagged drebrin A at postsynaptic sitse re-accumulate PSD-95. Over-expression of EGFP tagged drebrin A resulted in the enlargement of spines in mature neurons, but resulted in the formation of abnormal large protrusions in immature neurons. These results indicate that drebrin A accumulates spine-resident proteins via protein-protein interaction, and that clus tering of drebrin A play a key role in the morphological change from dendritic filopodia into mature spines.

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