Rapsyn mediates subsynaptic anchoring of PKA type I and stabilisation of acetylcholine receptor in vivo

Journal of Cell Science
Kyeong-Rok ChoiRüdiger Rudolf

Abstract

The stabilisation of acetylcholine receptors (AChRs) at the neuromuscular junction depends on muscle activity and the cooperative action of myosin Va and protein kinase A (PKA) type I. To execute its function, PKA has to be present in a subsynaptic microdomain where it is enriched by anchoring proteins. Here, we show that the AChR-associated protein, rapsyn, interacts with PKA type I in C2C12 and T-REx293 cells as well as in live mouse muscle beneath the neuromuscular junction. Molecular modelling, immunoprecipitation and bimolecular fluorescence complementation approaches identify an α-helical stretch of rapsyn to be crucial for binding to the dimerisation and docking domain of PKA type I. When expressed in live mouse muscle, a peptide encompassing the rapsyn α-helical sequence efficiently delocalises PKA type I from the neuromuscular junction. The same peptide, as well as a rapsyn construct lacking the α-helical domain, induces severe alteration of acetylcholine receptor turnover as well as fragmentation of synapses. This shows that rapsyn anchors PKA type I in close proximity to the postsynaptic membrane and suggests that this function is essential for synapse maintenance.

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Citations

Nov 22, 2013·PloS One·Isabel Martinez-Pena y ValenzuelaMohammed Akaaboune
Jan 7, 2016·Proceedings of the National Academy of Sciences of the United States of America·Muzamil Majid KhanRüdiger Rudolf
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Feb 13, 2021·Cells·Isabel Martinez-Pena Y Valenzuela, Mohammed Akaaboune
Sep 4, 2015·Journal of Cell Science·Mohamed AittalebMohammed Akaaboune

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