Phosphorylation in Presynaptic Plasticity – SRPK2 as a Relevant Kinase

Annika Mayer1, Julia Betzin1, Alexander Müller1, Ashley Waardenberg2, Albert Becker1, Mark Graham2, Dirk Dietrich3, Susanne Schoch1

1 Institute of Neuropathology and Department of Epileptology, University of Bonn Medical Center
2 Synapse Proteomics, Children’s Medical Research Institute, Westmead, Australia
3 Experimental Neurophysiology, Department Neurosurgery, University of Bonn Medical Center

Synaptic plasticity is the ability of synapses to adapt to activity- and experience-dependent changes by altering their strength and the efficacy of synaptic transmission. This synaptic strength can change short term as well as long term and thereby contribute to adaptions to sensory inputs as well as learning and memory. The phosphorylation states of synaptic proteins, especially those regulating vesicle exocytosis are presumably playing an important role in synaptic plasticity and whereas phosphorylation mechanisms on the postsynaptic site are well described, the role in presynaptic plasticity is still rather unknown. 

One kinase, which we recently found to trigger phosporylation of several presynaptic active zone proteins, is the Serine/Argenine-Rich Protein Kinase 2 (SRPK2), in particular RIM1, a presynaptic scaffolding protein essential for synaptic transmission and plasticity. Therefore, we tested whether the overexpression or knock-down of SRPK2 has an effect on basal synaptic transmission as well as on presynaptic plasticity. Using the genetically encoded glutamate sensor iGluSnFR, we showed that SRPK2 bidirectionally modifies synaptic vesicle release, requiring RIM1/2 expression. Silencing-induced increase in synaptic output, which we observed in untreated cultures, was occluded by elevated SRPK2 activity. Interestingly, SRPK2 knock-down showed also no significant increase in synaptic release. Using direct stochastic optical reconstruction microscopy (dSTORM) we observed that SRPK2 regulates the number of RIM1 nanoclusters in the active zone. This data suggests that SRPK2 is a presynaptic plasticity-relevant kinase enhancing local RIM1 availability at release sites and thereby mediating enhanced synaptic transmission.