Role of the visual experience-dependent nascent proteome in neuronal plasticity
- The Scripps Research Institute, United States
Abstract
Experience-dependent synaptic plasticity refines brain circuits during development. To identify novel protein synthesis-dependent mechanisms contributing to experience-dependent plasticity, we conducted a quantitative proteomic screen of the nascent proteome in response to visual experience in Xenopus optic tectum using bio-orthogonal metabolic labeling (BONCAT). We identified 83 differentially synthesized candidate plasticity proteins (CPPs). The CPPs form strongly interconnected networks and are annotated to a variety of biological functions, including RNA splicing, protein translation, and chromatin remodeling. Functional analysis of select CPPs revealed the requirement for eukaryotic initiation factor 3 subunit A (eIF3A), fused in sarcoma (FUS), and ribosomal protein s17 (RPS17) in experience-dependent structural plasticity in tectal neurons and behavioral plasticity in tadpoles. These results demonstrate that the nascent proteome is dynamic in response to visual experience and that de novo synthesis of machinery that regulates RNA splicing and protein translation is required for experience-dependent plasticity.
Data availability
-
Xenopus brainProteomeExchange number: PXD008659.
Article and author information
Author details
Funding
National Institutes of Health (EY011261)
- Han-Hsuan Liu
- Lucio Schiapparelli
- Wanhua Shen
- Hollis T Cline
National Institutes of Health (EY019005)
- Han-Hsuan Liu
- Lucio Schiapparelli
- Hollis T Cline
National Institutes of Health (MH067880)
- Daniel B Mcclatchy
- John R Yates
National Institutes of Health (MH100175)
- Daniel B Mcclatchy
- John R Yates
DartNeuroScience LLC
- Han-Hsuan Liu
- Hollis T Cline
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal protocols (#08-0083-4) were approved by the Institutional Animal Use and Care Committee of The Scripps Research Institute.
Copyright
© 2018, Liu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 2,416
- views
-
- 393
- downloads
-
- 21
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Role of the visual experience-dependent nascent proteome in neuronal plasticity
eLife 7:e33420.
https://doi.org/10.7554/eLife.33420
Further reading
-
- Neuroscience
Hydrostatic pressure is a dominant environmental cue for vertically migrating marine organisms but the physiological mechanisms of responding to pressure changes remain unclear. Here, we uncovered the cellular and circuit bases of a barokinetic response in the planktonic larva of the marine annelid Platynereis dumerilii. Increased pressure induced a rapid, graded, and adapting upward swimming response due to the faster beating of cilia in the head multiciliary band. By calcium imaging, we found that brain ciliary photoreceptors showed a graded response to pressure changes. The photoreceptors in animals mutant for ciliary opsin-1 had a smaller sensory compartment and mutant larvae showed diminished pressure responses. The ciliary photoreceptors synaptically connect to the head multiciliary band via serotonergic motoneurons. Genetic inhibition of the serotonergic cells blocked pressure-dependent increases in ciliary beating. We conclude that ciliary photoreceptors function as pressure sensors and activate ciliary beating through serotonergic signalling during barokinesis.
-
- Neuroscience
Synaptic heterogeneity is a hallmark of nervous systems that enables complex and adaptable communication in neural circuits. To understand circuit function, it is thus critical to determine the factors that contribute to the functional diversity of synapses. We investigated the contributions of voltage-gated calcium channel (VGCC) abundance, spatial organization, and subunit composition to synapse diversity among and between synapses formed by two closely related Drosophila glutamatergic motor neurons with distinct neurotransmitter release probabilities (Pr). Surprisingly, VGCC levels are highly predictive of heterogeneous Pr among individual synapses of either low- or high-Pr inputs, but not between inputs. We find that the same number of VGCCs are more densely organized at high-Pr synapses, consistent with tighter VGCC-synaptic vesicle coupling. We generated endogenously tagged lines to investigate VGCC subunits in vivo and found that the α2δ–3 subunit Straightjacket along with the CAST/ELKS active zone (AZ) protein Bruchpilot, both key regulators of VGCCs, are less abundant at high-Pr inputs, yet positively correlate with Pr among synapses formed by either input. Consistently, both Straightjacket and Bruchpilot levels are dynamically increased across AZs of both inputs when neurotransmitter release is potentiated to maintain stable communication following glutamate receptor inhibition. Together, these findings suggest a model in which VGCC and AZ protein abundance intersects with input-specific spatial and molecular organization to shape the functional diversity of synapses.
