A plasma membrane Ca2+ ATPase isoform at the postsynaptic density

Most excitatory input in the hippocampus impinges on dendritic spines. Entry of Ca2+ into spines through NMDA receptors can trigger a sequence of biochemical reactions leading to sustained changes in synaptic efficacy. To provide specificity, dendritic spines restrict the diffusion of Ca2+ signaling and downstream molecules. The postsynaptic density (PSD) (the most prominent subdomain within the spine) is the site of Ca2+ entry through NMDA receptors. We here demonstrate that Ca2+ can also be removed via pumps embedded in the PSD. Using light- and electron-microscopic immunohistochemistry, we find that PMCA2w, a member of the plasma membrane Ca2+-ATPase (PMCA) family, concentrates at the PSD of most hippocampal spines. We propose that PMCA2w may be recruited into supramolecular complexes at the postsynaptic density, thus helping to regulate Ca2+ nanodomains at subsynaptic sites. Taken together, these results suggest a novel function for PMCAs as modulators of Ca2+ signaling at the synapse.