Myosin Va cooperates with PKA RIalpha to mediate maintenance of the endplate in vivo.
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.
Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.
Ira V
IV
Röder
Kyeong-Rock
KR
Choi
Markus
M
Reischl
Yvonne
Y
Petersen
Markus E
ME
Diefenbacher
Manuela
M
Zaccolo
Tullio
T
Pozzan
Rüdiger
R
Rudolf
D054758:A Kinase Anchor Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / Q000235:genetics / Q000378:metabolism*; D003714:Denervation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D020409:Molecular Motor Proteins / Q000378:metabolism; D009045:Motor Endplate / Q000187:drug effects / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000037:antagonists & inhibitors / Q000378:metabolism*; D024701:Myosin Type V / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009473:Neuronal Plasticity; D011950:Receptors, Cholinergic / Q000378:metabolism; D015398:Signal Transduction
D054758:A Kinase Anchor Proteins; D000199:Actins; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D020409:Molecular Motor Proteins; C513082:Myo5a protein, mouse; D011950:Receptors, Cholinergic; D000242:Cyclic AMP; D024701:Myosin Type V; D018995:Myosin Heavy Chains; D015740:Calcitonin Gene-Related Peptide