1. Effects of DeSUMOylated Spastin on AMPA Receptor Surface Delivery and Synaptic Function Are Enhanced by Phosphorylating at Ser210.
- Author
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Zhang W, Zhang J, Zhang Z, Cha S, Li J, Chen L, Wu J, Teng J, Guo G, and Zhang J
- Subjects
- Animals, Phosphorylation, Dendritic Spines metabolism, Serine metabolism, Sumoylation, Neurons metabolism, Humans, Excitatory Postsynaptic Potentials drug effects, Excitatory Postsynaptic Potentials physiology, Cells, Cultured, Rats, Sprague-Dawley, HEK293 Cells, Cell Membrane metabolism, Protein Transport drug effects, Rats, Receptors, AMPA metabolism, Synapses metabolism, Hippocampus metabolism
- Abstract
Surface trafficking of AMPA receptors (AMPARs) is one of the important mechanisms mediating synaptic plasticity which is essential for cognitive functions such as learning and memory. Spastin, as a novel binding partner for the AMPAR, has been reported to regulate AMPAR surface expression and synaptic function. Additionally, Spastin undergoes two posttranslational modifications, phosphorylation and SUMOylation, both of which are crucial for synaptic function. However, gaps exist in our knowledge of how Spastin phosphorylation cross-talks with its SUMOylation in the regulation of AMPAR surface expression and synaptic function. Here, we reported that deSUMOylation of Spastin at Lys427 increased the surface level of AMPAR GluA2 subunit, the amplitude and frequency of miniature excitatory synaptic currents (mEPSC), and facilitated the morphological maturation of dendritic spines in cultured hippocampal neurons. Further studies demonstrated that Spastin phosphorylation at Ser210 further increased the enhancement of GluA2 surface expression and synaptic function by deSUMOylated Spastin, while dephosphorylation had the opposite effect. Simultaneously, deSUMOylation at Lys427 significantly increased the promoting effect of Spastin phosphorylation on synaptic function. In conclusion, our study suggests that cooperative interactions between phosphorylated and deSUMOylated Spastin are novel pathways to enhance synaptic function., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2024
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