The emergence of drebrin A at newly forming synapses

Chiye Aoki

Abstract

Drebrin A is a neuron-specific, actin-binding protein. Evidence supporting the involvement of drebrin A in synaptogenesis is mounting, but this body of work relies mostly on in vitro assays. In order to determine whether drebrin A arrives at the plasma membrane of neurons, in vivo, in time to orchestrate synaptogenesis, a new antibody was used to locate drebrin A in relation to electron microscopically imaged synapses. Western-blotting showed that drebrin A emerges at postnatal day (PNd) 6, and becomes progressively more associated with F-actin in the pellet fraction. Light microscopy showed high concentrations of drebrin A in the hippocampus and cortex. Electron microscopy revealed that drebrin A in these regions is located almost exclusively in dendrites both neonatally and in adulthood. In adulthood, nearly all of the synaptic drebrin A is within spines forming asymmetric, non-GABAergic, i.e., excitatory synapses. At PNd7, patches of drebrin A-immunoreactivity were discretely localized to the submembranous surfaces of dendrites forming slight protrusions. The drebrin A-sites exhibited only thin postsynaptic densities (PSD) but were already immunoreactive for the NR2B subunit of NMDA receptors. These drebrin A-sites lacked axonal associations or were contacted by axons that were immuno-negative for GABA and contained only a few vesicles. This, together with the selective association of drebrin A with asymmetric synapses in adulthood, indicates that the neonatal drebrin A-sites are precursors of excitatory synapses. Drebrin A may be involved in organizing the dendritic pool of actin for the formation of spines and of axo-spinous excitatory synapses.

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