F-Actin depolymerization and its role in translocation of protein into dendritic spines.

OUYANG, Y ; CAPANI, F. ; ROSENSTEIN, A.

Orlando

Congreso; Society for Neuroscience 2002; 2002

Actin is highly concentrated in dendritic spines of neurons. The functional significance of actin in dendritic spines is under investigation. In this study, we focus on a possible role of F-actin in translocation of protein into dendritic spines. Our hypothesis is that F-actin in its steady state may form a barrier to block translocation of proteins into dendritic spines. We have found that translocation of GFP-CaMKII into dendritic spines of cultured neurons (triggered with application of neurotransmitters) can be blocked after stabilize F-actin with 50 µM jasplakinolide for 3 hours. Furthermore, diffusion of a 3kD dextran into dendritic spines (15 min after neurons patched with electrodes fill with 3kD dextran) was also inhibited after the stabilization of F-actin. Both of these studies suggest that within dendritic spines, barriers for translocation of large molecules may be formed after F-actin stabilization. In addition, we have found that the labeling of F-actin decreased 30 min after induction of LTP by tetanic stimulation in hippocampal slices. The decrease can be blocked by application of APV, an inhibitor of NMDA receptors. EM observation revealed that more dendritic spines were lack of massive labeling of F-actin after induction of LTP. Taken together, the data suggests that the potentiated spines are open for translocation of proteins after tetanic stimulations but may be closed for translocation in control conditions. Our conclusion is that translocation of protein into dendritic spines may require depolymerization of F-actin from its steady state. This regulation may be an essential part of the mechanism of synaptic specificity of protein translocation.