title: PKC and PKA regulate AChR dynamics at the neuromuscular junction of living mice.
abstract: The steady state of the acetylcholine receptor (AChR) density at the neuromuscular junction (NMJ) is critical for efficient and reliable synaptic transmission. However, little is known about signaling molecules involved in regulating the equilibrium between the removal and insertion of AChRs that establishes a stable postsynaptic receptor density over time. In this work, we tested the effect of activities of two serine/threonine kinases, PKC and PKA, on the removal rate of AChRs from and the re-insertion rate of internalized recycled AChRs into synaptic sites of innervated and denervated NMJs of living mice. Using an in vivo time-lapse imaging approach and various pharmacological agents, we showed that PKC and PKA activities have antagonistic effects on the removal and recycling of AChRs. Inhibition of PKC activity or activation of PKA largely prevents the removal of pre-existing AChRs and promotes the recycling of internalized AChRs into the postsynaptic membrane. In contrast, stimulation of PKC or inactivation of PKA significantly accelerates the removal of postsynaptic AChRs and depresses AChR recycling. These results indicate that a balance between PKA and PKC activities may be critical for the maintenance of the postsynaptic receptor density.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Isabel
authors.initials: I
authors.lastname: Martinez-Pena y Valenzuela
authors.forename: Marcelo
authors.initials: M
authors.lastname: Pires-Oliveira
authors.forename: Mohammed
authors.initials: M
authors.lastname: Akaaboune
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020536:Enzyme Activators / Q000494:pharmacology; D005260:Female; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D009121:Muscle Denervation; D009281:Naphthalenes / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism*; D057907:Post-Synaptic Density; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D011950:Receptors, Cholinergic / Q000235:genetics / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D009435:Synaptic Transmission; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D059008:Time-Lapse Imaging
chemical_list: D020536:Enzyme Activators; D007546:Isoquinolines; D009281:Naphthalenes; D047428:Protein Kinase Inhibitors; D011950:Receptors, Cholinergic; D013449:Sulfonamides; D015124:8-Bromo Cyclic Adenosine Monophosphate; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; C058819:calphostin C; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D013755:Tetradecanoylphorbol Acetate