Abstract
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 RIMS1045E. 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.
Originalsprog | Engelsk |
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Artikelnummer | 110696 |
Tidsskrift | Cell Reports |
Vol/bind | 39 |
Udgave nummer | 3 |
ISSN | 2211-1247 |
DOI | |
Status | Udgivet - 19 apr. 2022 |
Bibliografisk note
Funding Information:We are grateful to M. Missler for help with EM sample preparation, Karen van Loo for assistance with GO analysis, and M. Geyer and R. Düster for technical assistance with in vitro phosphorylation assays. Our work was supported by the German Research Foundation (SFB1089, SP1775, and SCHO 820/4-7 to S.S. and D.D. and INST1172 15, DI853/3-5 and -7 and INST 217/785-1 to D.D.), the BONFOR program of the University of Bonn Medical Center (to S.S. and D.D.), a National Health and Medical Research Project Grant (1079160 to M.E.G.), the Cancer Institute New South Wales and the Australian Cancer Research Foundation, Australia (to M.E.G.). We would like to acknowledge the assistance of the Imaging, Proteomics, and Viral Core Facilities (supported by SFB1089) of the University Hospital Bonn. We thank S. Opitz, P. Trebing, and K. Krischer for excellent technical assistance. We acknowledge the support of the Children's Medical Research Institute Biomedical Proteomics Facility. Conceptualization, S.S. and D.D.; experimental design, J.A.M. J.B. M.E.G. D.D. and S.S.; investigation, J.A.M. J.B. K.E.-K. A.-M.O. A.M. I.P. J.S.-T. E.S. P.G. and J.R.W.; data analysis, J.A.M. J.B. A.-M.O. A.M. I.P. E.S. P.G. A.J.W. M.E.G. L.J.G. and T.D.M.; software development, T.D.M. L.J.G. and D.D.; supervision, A.J.B. M.E.G. D.D. and S.S.; funding acquisition, A.J.B. A.L. A.J.W. M.E.G. D.D. and S.S. J.A.M. J.B. A.J.W. M.E.G. D.D. and S.S. designed figures and wrote the manuscript with input from all authors. The authors declare no competing interests.
Funding Information:
We are grateful to M. Missler for help with EM sample preparation, Karen van Loo for assistance with GO analysis, and M. Geyer and R. Düster for technical assistance with in vitro phosphorylation assays. Our work was supported by the German Research Foundation (SFB1089, SP1775, and SCHO 820/4-7 to S.S. and D.D. and INST1172 15, DI853/3-5 and -7 and INST 217/785-1 to D.D.), the BONFOR program of the University of Bonn Medical Center (to S.S. and D.D.), a National Health and Medical Research Project Grant ( 1079160 to M.E.G.), the Cancer Institute New South Wales and the Australian Cancer Research Foundation, Australia (to M.E.G.). We would like to acknowledge the assistance of the Imaging, Proteomics, and Viral Core Facilities (supported by SFB1089) of the University Hospital Bonn . We thank S. Opitz, P. Trebing, and K. Krischer for excellent technical assistance. We acknowledge the support of the Children’s Medical Research Institute Biomedical Proteomics Facility.
Publisher Copyright:
© 2022 The Authors