The actin-modulating protein Synaptopodin mediates long-term survival of dendritic spines

Large spines are stable and important for memory trace formation. The majority of large spines also contains Synaptopodin (SP), an actin-modulating and plasticity-related protein. Since SP stabilizes F-actin, we speculated that the presence of SP within large spines could explain their long lifetime. Indeed, using time-lapse 2-photon-imaging of SP-transgenic granule cells in mouse organotypic tissue cultures we found that spines containing SP survived considerably longer than spines of equal size without SP. Of note, SP-positive spines that underwent pruning first lost SP before disappearing. Whereas the survival time courses of SP-positive (SP+) spines followed conditional two-phase decay functions, SP-negative (SP-) spines and all spines of SP-deficient animals showed single exponential decays. These results implicate SP as a major regulator of long-term spine stability: SP clusters stabilize spines and the presence of SP indicates spines of high stability.