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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.

Original publication




Journal article


J Cell Sci

Publication Date





714 - 723


Amino Acid Sequence, Animals, Cell Line, Cyclic AMP-Dependent Protein Kinase Type I, HEK293 Cells, Humans, Mice, Mice, Inbred C57BL, Models, Molecular, Molecular Sequence Data, Muscle Proteins, Muscle, Skeletal, Neuromuscular Junction, Protein Interaction Domains and Motifs, Protein Stability, Protein Structure, Secondary, Receptors, Cholinergic, Sequence Homology, Amino Acid, Synapses