RT Journal Article
SR Electronic
T1 Rapsyn mediates subsynaptic anchoring of PKA type I and stabilisation of acetylcholine receptor in vivo
JF Journal of Cell Science
JO J. Cell Sci.
FD The Company of Biologists Ltd
SP 714
OP 723
DO 10.1242/jcs.092361
VO 125
IS 3
A1 Choi, Kyeong-Rok
A1 Berrera, Marco
A1 Reischl, Markus
A1 Strack, Siegfried
A1 Albrizio, Marina
A1 Röder, Ira V.
A1 Wagner, Anika
A1 Petersen, Yvonne
A1 Hafner, Mathias
A1 Zaccolo, Manuela
A1 Rudolf, Rüdiger
YR 2012
UL http://jcs.biologists.org/content/125/3/714.abstract
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.