Postsynaptic Transport Packets

Philip E. Washbourne*


To understand the molecular methods by which synapse formation occurs, it is critical to know the mechanisms by which all the synaptic components can possibly arrive at a newly forming synapse. Methods of trafficking can range from diffusion through the cytoplasm or in the plasma membrane to exo/endocytic cycling between bouts of transport along microtubules. In the case of the post-synaptic density (PSD) of glutamatergic synapses, it appears that many of the necessary proteins arrive separately and by different means. Here we examine the modes of transport and recruitment of a number of postsynaptic components to newly forming, glutamatergic synapses.


The postsynaptic compartment is the region of the synapse specialized in receiving neurotransmitter secreted by the presynaptic terminal. This neuronal subdomain contains not only receptors which bind and sense the neurotransmitter, but also molecules required for signaling, scaffolding, and adhesion with the presynaptic neuron1. The best-studied postsynaptic compartment is at the glutamatergic synapse. This is probably due to the fact that the postsynaptic specialization of glutamatergic synapses is easily recognizable in electron micrographs as a dense material under the membrane, hence the name PSD. Another reason lies in the variety of glutamate receptor types and their respective potential roles in learning and memory.

In order to understand how the glutamatergic PSD forms, it is crucial to know its composition2,3 and where its components are synthesized and located prior to synapse formation and how they get to new sites of synapse formation. Knowledge of the trafficking of PSD proteins will ultimately lead to the comprehension of mechanisms of molecular recruitment to nascent postsynaptic sites.

'Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA; [email protected]

The largest advance in understanding molecular trafficking of synaptic proteins happened during the late 1990s with the advent of high-resolution time-lapse imaging and the tagging of synaptic components with fluorescent proteins such as green fluorescent protein4. Prior to these techniques, our understanding of postsynaptic molecule trafficking relied on data obtained using fixed specimens such as electron micrographs5 and immunofluorescence images6 or on data from electrophysiological recordings7,8. While the former two only provide static snapshots of protein distribution during development, the latter does not resolve the localization of receptors prior to insertion in the plasma membrane. Furthermore, electrophysiological recordings tell us nothing of the localization of intracellular postsynaptic proteins that do not directly influence channel properties. Despite the constraints of these early studies, they have shown that (1) postsynaptic molecules redistribute from a nonsynaptic dendritic localization to a synaptic localization5-8 and (2) some postsynaptic molecules such as NMDA and AMPA-type glutamate receptors and the postsynaptic scaffolding protein PSD-95 are localized in nonsynaptic clusters prior to synapse formation6,9.

The observation of nonsynaptic glutamate receptor and PSD-95 clusters led immediately to the question as to what these protein clusters may represent. Were they reservoirs of proteins that could then diffuse to new sites of synapse formation or did they perhaps represent a transport unit? Furthermore, the lack of colocalization of the nonsynaptic clusters of NMDA receptors, PSD-95, and AMPA receptors6 suggested that assembly of the PSD may contrast starkly with formation of the presynaptic terminal10,11. It had been discovered that, at the developing presynaptic terminal, complexes containing a number of active zone and synaptic vesicle components are recruited on a rapid time scale to generate a functional presynaptic compartment11-13 (discussed in more detail in Chapter 15). On the postsynaptic side, however, the dynamics of synaptic proteins has been controversial.

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