Protein phosphatase 2b dual function facilitates synaptic integrity and motor learning

Zhanmin Lin, Bin Wu, Maarten W. Paul, Ka Wan Li, Yao Yao, Ihor Smal, Martina Proietti Onori, Hana Hasanbegovic, Karel Bezstarosti, Jeroen Demmers, Adriaan B. Houtsmuller, Erik Meijering, Freek E. Hoebeek, Martijn Schonewille, August B. Smit*, Zhenyu Gao, Chris I. de Zeeuw

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Protein phosphatase 2B (PP2B) is critical for synaptic plasticity and learning, but the molecular mechanisms involved remain unclear. Here we identified different types of proteins that interact with PP2B, including various structural proteins of the postsynaptic densities (PSDs) of Purkinje cells (PCs) in mice. Deleting PP2B reduced expression of PSD proteins and the relative thickness of PSD at the parallel fiber to PC synapses, whereas reexpression of inactive PP2B partly restored the impaired distribution of nanoclusters of PSD proteins, together indicating a structural role of PP2B. In contrast, lateral mobility of surface glutamate receptors solely depended on PP2B phosphatase activity. Finally, the level of motor learning covaried with both the enzymatic and nonenzymatic functions of PP2B. Thus, PP2B controls synaptic function and learning both through its action as a phosphatase and as a structural protein that facilitates synapse integrity.

Original languageEnglish
Pages (from-to)5579-5594
Number of pages16
JournalJournal of Neuroscience
Issue number26
Publication statusPublished - 30 Jun 2021

Bibliographical note

Funding Information:
This work was supported by EUR fellowship, Erasmus MC fellowship, NWO VENI, VIDI, and NWO-Klein grants to Z.G.; and ERC, ZonMw, NWO-ALW, ENW-Klein, Medical NeuroDelta, NIN VriendenFonds Albinisme grant, and LSH-NWO INTENSE to C.I.D.Z. We thank Mandy Rutteman and Laura Post for maintaining mouse breeding; and Elize Haasdijk and Erika Goedknegt for assistance in histology and EM. The authors declare no competing financial interests.

Publisher Copyright:
© 2021 Lin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.


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