Sofia Ainatzi, Svenja V Kaufmann, Ivan Silbern, Svilen V Georgiev, Sonja Lorenz, Silvio O Rizzoli, Henning Urlaub
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Ca2+-triggered (de)ubiquitination events in synapses.
Neuronal communication relies on neurotransmitter release from synaptic vesicles (SVs), whose dynamics are controlled by Ca2+-dependent pathways, as many thoroughly studied phosphorylation cascades. However, little is known about other post-translational modifications, as ubiquitination. To address this, we analysed resting and stimulated synaptosomes (isolated synapses) by quantitative mass spectrometry. We identified more than 5,000 ubiquitination sites on ∼2,000 proteins, the majority of which participate in SV recycling processes. Several proteins showed significant changes in ubiquitination in response to Ca2+ influx, with the most pronounced changes in CaMKIIα and the clathrin adaptor protein AP180. To validate this finding, we generated a CaMKIIα mutant lacking the ubiquitination target site (K291) and analysed it both in neurons and non-neuronal cells. K291 ubiquitination, close to an important site for CaMKIIα autophosphorylation (T286), influences the synaptic function of this kinase. We suggest that ubiquitination in response to synaptic activity is an important regulator of synaptic function.
期刊介绍：
The mission of MCP is to foster the development and applications of proteomics in both basic and translational research. MCP will publish manuscripts that report significant new biological or clinical discoveries underpinned by proteomic observations across all kingdoms of life. Manuscripts must define the biological roles played by the proteins investigated or their mechanisms of action.
The journal also emphasizes articles that describe innovative new computational methods and technological advancements that will enable future discoveries. Manuscripts describing such approaches do not have to include a solution to a biological problem, but must demonstrate that the technology works as described, is reproducible and is appropriate to uncover yet unknown protein/proteome function or properties using relevant model systems or publicly available data.
Scope:
-Fundamental studies in biology, including integrative "omics" studies, that provide mechanistic insights
-Novel experimental and computational technologies
-Proteogenomic data integration and analysis that enable greater understanding of physiology and disease processes
-Pathway and network analyses of signaling that focus on the roles of post-translational modifications
-Studies of proteome dynamics and quality controls, and their roles in disease
-Studies of evolutionary processes effecting proteome dynamics, quality and regulation
-Chemical proteomics, including mechanisms of drug action
-Proteomics of the immune system and antigen presentation/recognition
-Microbiome proteomics, host-microbe and host-pathogen interactions, and their roles in health and disease
-Clinical and translational studies of human diseases
-Metabolomics to understand functional connections between genes, proteins and phenotypes
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