Synaptic activity and strength are reflected by changes in the post-synaptic secretory pathway

Clara-Marie Gürth,Silvio O Rizzoli,Tal M Dankovich,Elisa D’Este

doi:10.1038/s41598-020-77260-2

Abstract

Neurons are highly asymmetric cells that span long distances and need to react promptly to local demands. Consequently, neuronal secretory pathway elements are distributed throughout neurites, specifically in post-synaptic compartments, to enable local protein synthesis and delivery. Whether and how changes in local synaptic activity correlate to post-synaptic secretory elements is still unclear. To assess this, we used STED nanoscopy and automated quantitative image analysis of post-synaptic markers of the endoplasmic reticulum, ER-Golgi intermediate compartment, trans-Golgi network, and spine apparatus. We found that the distribution of these proteins was dependent on pre-synaptic activity, measured as the amount of recycling vesicles. Moreover, their abundance correlated to both pre- and post-synaptic markers of synaptic strength. Overall, the results suggest that in small, low-activity synapses the secretory pathway components are tightly clustered in the synaptic area, presumably to enable rapid local responses, while bigger synapses utilise secretory machinery components from larger, more diffuse areas.

Highlights

Neurons are highly asymmetric cells that span long distances and need to react promptly to local demands
While the synaptopodin signal was clearly concentrated in the spine head, calreticulin, ERGIC53 and TGN38 appeared as sparse, but distinct, spots in both the dendritic shaft and spines
We investigated the correlations between the abundance and distribution of calreticulin, ERGIC53 (ER-Golgi intermediate compartment marker), TGN38, and synaptopodin, and the pre-synaptic markers vGLUT1 or SYT1, as well as the post-synaptic marker homer

Summary

Introduction

Neurons are highly asymmetric cells that span long distances and need to react promptly to local demands. The secretory pathway elements support cellular functions by ensuring local delivery and post-translational modifications of secreted and transmembrane proteins These proteins are translated directly into the endoplasmic reticulum (ER) lumen, and transported to the Golgi apparatus via the ER-Golgi intermediate compartment (ERGIC)[1,2]. Cargoes exit the Golgi apparatus via the trans-Golgi network (TGN), where the proteins are sorted and transported to their respective sites of action[3] Due to their highly asymmetrical shape, size and subcellular specialisation, neurons need to organise protein synthesis along their entire volume (for r eviews[4,5,6,7,8]). Trafficking of ERGIC vesicles along dendrites is restricted by increased neuronal activity, indicating that this post-ER compartment can be subjected to synaptic activity-dependent r egulation[29]

Methods

Results

Conclusion