ISOFORM SPECIFICITY IN THE RELATIONSHIP OF ACTIN TO DENDRITIC SPINES

Dendritic spines contain high concentrations of actin, but neither the isoforms involved nor the mechanism of accumulation is known. In situ hybridization with specific probes established that beta- and gamma-c ytoplasmic actins are selectively expressed at high levels by spine-be aring neurons. Transfecting cultured hippocampal neurons with epitope- tagged actin isoforms showed that cytoplasmic beta- and gamma-cytoplas mic actins are correctly targeted to spines, whereas alpha-cardiac mus cle actin, which is normally absent from neurons, formed aggregates in dendrites. The transfected actin cDNAs contained only coding domains, suggesting that spine targeting involves amino acid sequences in the proteins, an interpretation supported by experiments with chimeric cDN As in which C-terminal actin sequences were found to be determinative in spine targeting. By contrast to actin, microtubule components, incl uding tubulin and MAP2, were restricted to the dendritic shaft domain. The close association of cytoplasmic actins with spines together with their general involvement in cell surface motility further supports t he idea that actin motility-based changes in spine shape may contribut e to synaptic plasticity.