Abstract
Dendritic spines are multiple functional units that receive most of excitatory inputs in central nervous system. We show here that a novel drebrin-binding protein is involved in the regulation of dendritic spine formation. Contrary to its predominant localization in the neculei of non-neuronal cells, this protein was localized primarily in nucleus and dendritic spines in neurons. Hence, we named it Spikar for its unique intracellular localization in spine and karyoplasm. Since drebrin A is a neuron-specific F-actin binding protein that regulates spine function and morphology, we analyzed whether Spikar plays a role in the dendritic spine formation. Transfection of shRNA expression vector into cultured hippocampal neurons resulted in ∼20% decrease in endogenous Spikar expression. When neurons were transfected at 3 days in vitro (DIV) and analyzed at 16 DIV, the neurons expressing Spikar shRNA (Spikar-KD neurons) showed lower densities of dendritic filopodia and dendritic spines than control cells. However, the spines formed in Spikar-KD neurons showed normal immunoreactivities of synaptic proteins. Miniature excitatory postsynaptic currents (mEPSCs) significantly reduced in Spikar-KD neurons without affecting the mEPSC amplitude. These results suggest that Spikar is involved in the dendritic spine formation but not in the functional maturation of the spines. [J Physiol Sci. 2007;57 Suppl:S147]