A presynaptic phosphosignaling hub for lasting homeostatic plasticity

• Published in: Cell reports (Cambridge) 2022-04, Vol.39 (3), p.110696-110696, Article 110696
• Main Authors: Müller, Johannes Alexander, Betzin, Julia, Santos-Tejedor, Jorge, Mayer, Annika, Oprişoreanu, Ana-Maria, Engholm-Keller, Kasper, Paulußen, Isabelle, Gulakova, Polina, McGovern, Terrence Daniel, Gschossman, Lena Johanna, Schönhense, Eva, Wark, Jesse R., Lamprecht, Alf, Becker, Albert J., Waardenberg, Ashley J., Graham, Mark E., Dietrich, Dirk, Schoch, Susanne
• Format: Article
• Language: English
• Subjects: active zone; Animals; GTP-Binding Proteins - metabolism; Homeostasis - physiology; homeostatic plasticity; KinSwing; Mammals - metabolism; Neuronal Plasticity - physiology; phosphoproteomics; phosphorylation; presynaptic plasticity; Presynaptic Terminals - metabolism; RIM1; SRSF protein kinase 2; Synapses - metabolism; synaptic transmission; Synaptic Transmission - physiology; Synaptic Vesicles - metabolism; vesicle release
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2022.110696

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. [Display omitted] •RIM is required for induction of presynaptic homeostatic plasticity (PHP)•The kinase SRPK2 regulates basal synaptic vesicle release and PHP•SRPK2 controls the number of RIM nanoclusters and of docked synaptic vesicles•Phosphorylation of RIM1 at serine 1045 increases release and occludes PHP The amount of neurotransmitters released in response to an action potential can be tuned by altering the number of release sites. Müller et al. show that the kinase SRPK2 is involved in regulating this process via the presynaptic active-zone protein RIM. Phosphorylation status changes of RIM dynamically modulate synaptic strength.