A Presynaptic Phosphosignaling Hub for Lasting Homeostatic Plasticity
Open accessAbstract
Stable function of networks requires that synapses adapt their strength to levels of neuronal activity, and failure to do so results in cognitive disorders. How such homeostatic regulation may be implemented in mammalian synapses remains poorly understood. Here we show that the phosphorylation status of several positions of the active-zone (AZ) protein RIM1 are relevant for synaptic glutamate release. Position RIMS1045 is necessary and sufficient for expression of silencing-induced homeostatic plasticity and is kept phosphorylated by serine arginine protein kinase 2 (SRPK2). SRPK2-induced upscaling of synaptic release leads to additional RIM1 nanoclusters and docked vesicles at the AZ and is not observed in the absence of RIM1 and occluded by RIM S1045E . Our data suggest that SRPK2 and RIM1 represent a presynaptic phosphosignaling hub that is involved in the homeostatic balance of synaptic coupling of neuronal networks.
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SRPK3 encodes a protein member of the serine/arginine-rich specific kinase family involved in mRNA processing, and synaptic vesicle and neurotransmitter release.
“SRPK3 encodes a protein member of the serine/arginine‐rich specific kinase family that is known to be involved in mRNA processing, and synaptic vesicle and neurotransmitter release.”
From Interstitial lung disease and pancreatic exocrine insufficiency in <scp>CADDS</scp>: Phenotypic expansion and literature review (2023) · cites this paper as [18]
The sections on the SRPK2-dependent phosphoproteome and RIM1-dependent release link SRPK2 to alternative splicing and neurotransmitter release. The claim attributes those roles to SRPK3, which these passages do not establish. (LLM, conf=0.85)
Experimental — accuracy not yet measuredPKA-dependent phosphorylation of RIM has been shown not to be involved in LTP, but recent evidence highlights the importance of other phosphorylation sites of RIM during plasticity.
“Although PKA-dependent phosphorylation of RIM has been shown not to be involved in LTP [94], recent evidence highlights the importance of other phosphorylation sites of RIM during plasticity [95].”
From Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons (2024) · cites this paper as [95]
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References 71 · Cited by 36
Research works printed but not linked: 12
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- Li-Cor Corporate Company https://www.licor.com/bio/ image-studio-lite/ Imaris Bitplane https://imaris.oxinst.com/packages EspINA Interactive Neuron Analyzer Cajal Blue Brain Project http://cajalbbp.es/espina/ MatLab MathWorks https://de.mathworks.com/ products/matlab.html phosphoprocessR (Version 0.99.8) Waardenberg AJ, 2017, Methods Mol Biol. doi: https://doi.org/10.1007/ 978-1-4939-6955-5_17 https://github.com/awaardenberg/ phosphoProcessR · DOI
- Authors
- Müller, J. A., Betzin, J., Santos-Tejedor, J., Mayer, A., Oprişoreanu, A.-M., Engholm-Keller, K., Paulußen, I., Gulakova, P., McGovern, T. D., Gschossman, L. J., Schönhense, E., Wark, J. R., Lamprecht, A., Becker, A. J., Waardenberg, A. J., Graham, M. E., Dietrich, D., & Schoch, S.
- Affiliations
- University Hospital Bonn (DE)
- The University of Sydney (AU)
- University of Bonn (DE)
- Australian Institute of Tropical Health and Medicine (AU)
- Corresponding author
- Dietrich, Dirk
- Schoch, Susanne
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2022-04
- Volume
- 39
- Issue
- 3
- Pages
- 110696
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W4226477612
- Cited by
- 36
- References
- 71
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 8 · 2023: 13 · 2022: 2 · 2021: 1
- FWCI
- 1.83
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- SSRN Electronic Journal (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- ResearchOnline at James Cook University (James Cook University) (submittedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion, cc-by-nc-nd)
- Funders
- National Health and Medical Research Council (1079160)
- Australian Cancer Research Foundation
- Cancer Institute NSW
- Deutsche Forschungsgemeinschaft
- BMBF Bonn
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- homeostatic plasticity, RIM1, SRPK2, active zone, docked vesicles, synaptic coupling, protein phosphorylation
- MeSH terms
- Animals, Homeostasis, Mammals, Synaptic Transmission, Neuronal Plasticity, Synapses, Synaptic Vesicles, Presynaptic Terminals, GTP-Binding Proteins
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