Myosin Va cooperates with PKA RIalpha to mediate maintenance of the endplate in vivo
| Autor: | Tullio Pozzan, Yvonne Petersen, Ira V. Röder, Rüdiger Rudolf, Manuela Zaccolo, Markus E. Diefenbacher, Markus Reischl, Kyeong-Rock Choi |
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| Rok vydání: | 2010 |
| Předmět: |
fluorescence sensors
Receptor recycling Calcitonin Gene-Related Peptide Cyclic AMP-Dependent Protein Kinase RIalpha Subunit Myosin Type V Skeletal muscle A Kinase Anchor Proteins Mice Transgenic AMPA receptor macromolecular substances Biology Motor Endplate Postsynapse QH345 Mice Postsynaptic potential cAMP Myosin Cyclic AMP Animals Receptors Cholinergic Actin Acetylcholine receptor Multidisciplinary Microscopy Confocal Neuronal Plasticity Myosin Heavy Chains Molecular Motor Proteins Biological Sciences Actin cytoskeleton Denervation Actins Cell biology Mice Inbred C57BL Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 107(5) |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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