PT  - JOURNAL ARTICLE
AU  - Choi, Kyeong-Rok
AU  - Berrera, Marco
AU  - Reischl, Markus
AU  - Strack, Siegfried
AU  - Albrizio, Marina
AU  - Röder, Ira V.
AU  - Wagner, Anika
AU  - Petersen, Yvonne
AU  - Hafner, Mathias
AU  - Zaccolo, Manuela
AU  - Rudolf, Rüdiger
TI  - Rapsyn mediates subsynaptic anchoring of PKA type I and stabilisation of acetylcholine receptor in vivo
AID  - 10.1242/jcs.092361
DP  - 2012 Feb 01
TA  - Journal of Cell Science
PG  - 714--723
VI  - 125
IP  - 3
4099  - http://jcs.biologists.org/content/125/3/714.short
4100  - http://jcs.biologists.org/content/125/3/714.full
SO  - J. Cell Sci.2012 Feb 01; 125
AB  - 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.