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Control of Transmembrane Protein Diffusion within the Postsynaptic Density Assessed by Simultaneous Single-Molecule
1Department of Physiology and Program in Neuroscience, University of Maryland School of Medicine Baltimore, MD, USA.
Frontiers in Synaptic Neuroscience
|August 9, 2016
Summary
Postsynaptic protein mobility is controlled by the density of scaffold proteins within nanodomains. Even without direct binding, crowding by scaffold molecules significantly slows transmembrane protein movement in synapses.
Area of Science:
- Neuroscience
- Cell Biology
- Biophysics
Background:
- Postsynaptic transmembrane proteins are crucial for synaptic function, mediating cell-cell contact and ion flux.
- The precise positioning and movement of these proteins within the postsynaptic density (PSD) are vital for synaptic plasticity and neurotransmission.
- Factors governing receptor mobility within synapses, particularly the impact of nanoscale organization, remain poorly understood.
Purpose of the Study:
- To experimentally investigate how the density of proteins within postsynaptic density nanodomains influences the mobility of transmembrane proteins.
- To determine the extent to which protein crowding, independent of direct binding interactions, affects receptor movement at the synapse.
Main Methods:
- Utilized single-molecule tracking via universal point accumulation-for-imaging-in-nanoscale-topography (uPAINT).
- Simultaneously resolved the internal structure of postsynaptic densities (PSDs) using photoactivated localization microscopy (PALM).
- Tracked transmembrane proteins within PSDs characterized by varying scaffold protein densities.
Main Results:
- Experimental evidence confirms that postsynaptic density scaffold protein density significantly impacts transmembrane protein mobility.
- Transmembrane proteins were observed to slow down in regions of high PSD-95 density, even without direct binding to PSD-95.
- These findings suggest that steric hindrance and crowding by scaffold molecules are sufficient to restrict receptor mobility.
Conclusions:
- Postsynaptic protein crowding within nanodomains is a key determinant of transmembrane protein mobility.
- Understanding PSD nanostructure and its influence on protein dynamics is critical, especially given links to neurological disorders.
- The combined PALM and uPAINT approach offers a powerful tool for studying protein-nano-environment interactions in synapses and beyond.
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