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A large-scale nanoscopy and biochemistry analysis of postsynaptic dendritic spines
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A large-scale nanoscopy and biochemistry analysis of postsynaptic dendritic spines
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Journal Article
A large-scale nanoscopy and biochemistry analysis of postsynaptic dendritic spines
2021
Overview
Dendritic spines, the postsynaptic compartments of excitatory neurotransmission, have different shapes classified from ‘stubby’ to ‘mushroom-like’. Whereas mushroom spines are essential for adult brain function, stubby spines disappear during brain maturation. It is still unclear whether and how they differ in protein composition. To address this, we combined electron microscopy and quantitative biochemistry with super-resolution microscopy to annotate more than 47,000 spines for more than 100 synaptic targets. Surprisingly, mushroom and stubby spines have similar average protein copy numbers and topologies. However, an analysis of the correlation of each protein to the postsynaptic density mass, used as a marker of synaptic strength, showed substantially more significant results for the mushroom spines. Secretion and trafficking proteins correlated particularly poorly to the strength of stubby spines. This suggests that stubby spines are less likely to adequately respond to dynamic changes in synaptic transmission than mushroom spines, which possibly explains their loss during brain maturation.
This work provides a first molecular view of dendritic spines, for both the mushroom and stubby classes, obtained by integrating electron microscopy, quantitative biochemistry, super-resolution microscopy and 3D molecular visualizations.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Animal Genetics and Genomics
/ Animals
/ Biomedical and Life Sciences
/ Brain
/ Dendritic Spines - metabolism
/ Dendritic Spines - ultrastructure
/ Methods
/ Microscopy, Electron, Transmission
/ Post-Synaptic Density - metabolism
/ Post-Synaptic Density - ultrastructure
/ Proteins
/ Proteome
/ Rats
/ Resource
/ Synaptic Transmission - physiology
/ Topology
