RT Journal Article
SR Electronic
T1 Myosin Va cooperates with PKA RIα to mediate maintenance of the endplate in vivo
JF Proceedings of the National Academy of Sciences
JO Proc Natl Acad Sci USA
FD National Academy of Sciences
SP 2031
OP 2036
DO 10.1073/pnas.0914087107
VO 107
IS 5
A1 Röder, Ira V.
A1 Choi, Kyeong-Rock
A1 Reischl, Markus
A1 Petersen, Yvonne
A1 Diefenbacher, Markus E.
A1 Zaccolo, Manuela
A1 Pozzan, Tullio
A1 Rudolf, Rüdiger
YR 2010
UL http://www.pnas.org/content/107/5/2031.abstract
AB Myosin V motor proteins facilitate recycling of synaptic receptors, including AMPA and acetylcholine receptors, in central and peripheral synapses, respectively. To shed light on the regulation of receptor recycling, we employed in vivo imaging of mouse neuromuscular synapses. We found that myosin Va cooperates with PKA on the postsynapse to maintain size and integrity of the synapse; this cooperation also regulated the lifetime of acetylcholine receptors. Myosin Va and PKA colocalized in subsynaptic enrichments. These accumulations were crucial for synaptic integrity and proper cAMP signaling, and were dependent on AKAP function, myosin Va, and an intact actin cytoskeleton. The neuropeptide and cAMP agonist, calcitonin-gene related peptide, rescued fragmentation of synapses upon denervation. We hypothesize that neuronal ligands trigger local activation of PKA, which in turn controls synaptic integrity and turnover of receptors. To this end, myosin Va mediates correct positioning of PKA in a postsynaptic microdomain, presumably by tethering PKA to the actin cytoskeleton.