Activity-dependent protein transport as a synaptic tag

The "synaptic tagging and capture" hypothesis proposed that a hypothetical, cell biological mark is activated in the synapses undergoing earlyphase plasticity. Newly synthesized plasticity-related proteins (PRPs) are assumed to establish late plasticity only in the marked synapses after unspecifi c transport along dendrites from soma. Demonstration of the "synaptic tagging and capture" hypothesis will be achieved by showing that a specifi c cell biological activity regulates behaviors of an exemplifying PRP in accordance with several unique characteristics assumed by the original hypothesis. We hypothesized that synaptic activity affects synaptic localization of PRPs on transport, namely, active spines receive PRPs, while no transport to inactive spines. We observed transport of Vesl-1S (also called Homer-1a) protein, one of PRPs, by measuring fl uorescence of fused protein with EGFP (VE) in spines, and found that somatic Vesl-1S protein prevailed in most dendritic branches, and was translocated into spines where NMDA receptors were activated. The NMDA receptor-dependent translocation of VE protein from dendrite to spine fulfilled many of the hypothesized conditions of synaptic tagging, demonstrating the synaptic tagging hypothesis with Vesl-1S as an exemplifying PRP. In addition to summarizing our findings, we would like to discuss the relevance of synaptic tagging as an input-specifi city mechanism of late plasticity. An inputspecifi city mechanism restricts synapses where the expression mechanism of plasticity is activated. An essential feature of late plasticity is that it depends on synaptic functions of multiple PRPs, which is newly synthesized in various loci and lags. Late expression mechanism may require integrated functions of multiple PRPs, each of which likely has distinct localization, regulation, and function in the synapse. Synaptic tagging is a mechanism that allows synapse-specific function of PRPs thereby assumed as a late input-specificity mechanism. Considering diversity in cell biological and biochemical properties of PRPs, it is suggested that multiple cell biological activities work as synaptic tagging, each of which is specifi c to a subset of PRPs and differently regulates synaptic localization and function of the PRPs at distinct timing. Activity-dependent spine translocation of Vesl-1S/Homer-1a may be an example of the diverse spectrum of synaptic tagging mechanisms.