Activity-dependent protein transport as a synaptic tag

The "synaptic tagging and capture" hypothesis proposes that a hypothetical, cell biological mark is activated in the synapses undergoing early-phase plasticity. Newly synthesized plasticity-related proteins (PRPs) are assumed to establish late plasticity only in the marked synapses after unspecific transport along dendrites from soma. Demonstration of the "synaptic tagging and capture" hypothesis will be achieved by showing that a specific 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 inactive spines do not. We observed the transport of Vesl-1S (also called Homer-1a) protein, one of the PRPs, by measuring the fluorescence 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-specificity mechanism of late plasticity. An input-specificity mechanism restricts synapses where the expression mechanism of plasticity is activated. An essential feature of late plasticity is that it depends on the synaptic functions of multiple PRPs, which are newly synthesized in various loci and lags. Late expression mechanisms 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 the synapse-specific function of PRPs, thereby assuming it as a late input-specificity mechanism. Considering the 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 specific to a subset of PRPs and differently regulates synaptic localization and function of the PRPs at distinct timings. Activity-dependent spine translocation of Vesl-1S/Homer-1a may be an example of the diverse spectrum of synaptic tagging mechanisms.