Abstract
The dynamic exchange of neurotransmitter receptors at synapses relies on their lateral diffusion in the plasma membrane. At synapses located on dendritic spines this process is limited by the geometry of the spine neck that restricts the passage of membrane proteins. Biochemical compartmentalisation of the spine is believed to underlie the input-specificity of excitatory synapses and to set the scale on which functional changes can occur. Synaptopodin is located predominantly in the neck of dendritic spines, and is thus ideally placed to regulate the exchange of synaptic membrane proteins. The central aim of our study was to assess whether the presence of synaptopodin influences the mobility of membrane proteins in the spine neck and to characterise whether this was due to direct molecular interactions or to spatial constraints that are related to the structural organisation of the neck. Using single particle tracking we have identified a specific effect of synaptopodin on the diffusion of metabotropic mGluR5 receptors in the spine neck. However, super-resolution STORM/PALM imaging showed that this was not due to direct interactions between the two proteins, but that the presence of synaptopodin is associated with an altered local organisation of the F-actin cytoskeleton, that in turn could restrict the diffusion of membrane proteins with large intracellular domains through the spine neck. This study contributes new data on the way in which the spine neck compartmentalises excitatory synapses. Our data complement models that consider the impact of the spine neck as a function of its shape, by showing that the internal organisation of the neck imposes additional physical barriers to membrane protein diffusion.
Highlights
The majority of excitatory synapses in the central nervous system are contained within dendritic protrusions called spines
The neck of dendritic spines acts as a diffusion barrier that separates the site of synaptic transmission in the spine head from the remainder of the dendrite [1]
The thin spine neck limits the recruitment of synaptic components as well as their escape from the spine head, which has consequences for the plasticity of spiny synapses, both in terms of input-specificity and regarding the extent of any molecular changes that can occur
Summary
The majority of excitatory synapses in the central nervous system are contained within dendritic protrusions called spines. The separation of the site of synaptic transmission from the dendritic shaft allows synapse-specific inputs and signal processing. This compartmentalisation relies critically on the geometry of the thin spine neck that connects the spine head with the dendrite (discussed in [1]). While some controversy remains regarding the role of spines for the electric compartmentalisation of the synapse [2,3], it has become clear that the spine neck creates a barrier to the diffusion of synaptic components [4,5]), including membrane. While some controversy remains regarding the role of spines for the electric compartmentalisation of the synapse [2,3], it has become clear that the spine neck creates a barrier to the diffusion of synaptic components (e.g. [4,5]), including membrane
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