Myosin va cooperates with PKA RIα to mediate maintenance of the endplate in vivo

Roder, I.V., Choi, K.R., Reischl, M., Petersen, Y., Diefenbacher, M.E., Zaccolo, M., Pozzan, T. and Rudolf, R. (2010) Myosin va cooperates with PKA RIα to mediate maintenance of the endplate in vivo. Proceedings of the National Academy of Sciences of the United States of America, 107(5), pp. 2031-2036. (doi: 10.1073/pnas.0914087107)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Zaccolo, Professor Manuela
• Authors: Roder, I.V., Choi, K.R., Reischl, M., Petersen, Y., Diefenbacher, M.E., Zaccolo, M., Pozzan, T., and Rudolf, R.
• Subjects: Q Science > QH Natural history > QH345 Biochemistry
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Proceedings of the National Academy of Sciences of the United States of America
• Journal Abbr.: Proc. Natl. Acad. Sci.
• Publisher: National Academy of Sciences
• ISSN: 0027-8424
• ISSN (Online): 1091-6490
• Published Online: 19 January 2010