title: Decreased phosphorylation of δ and ε subunits of the acetylcholine receptor coincides with delayed postsynaptic maturation in PKC θ deficient mouse.
abstract: Protein kinase C (PKC) activity is involved in the nicotinic acetylcholine receptor (nAChR) redistribution at the neuromuscular junction in vivo during postnatal maturation. Here we studied, in PKC theta (PKCtheta) deficient mice (KO), how the theta isoform of PKC is involved in the nAChR cluster maturation that is accompanied by the developmental activity-dependent neuromuscular synapse elimination process. We found that axonal elimination and dispersion of nAChR from the postsynaptic plaques and its redistribution to form the mature postsynaptic apparatus were delayed but not totally suppressed in PKCtheta deficient mice. Moreover, the delay in the maturation of the morphology of the nAChR clusters during the early postnatal synapse elimination period in the PKCtheta deficient mice coincides with a reduction in the PKCtheta-mediated phosphorylation on the delta subunit of the nAChR. In addition, we show evidence for PKCtheta regulation of PKA in normally phosphorylating the epsilon subunit of nAChR. We have also found that the theta isoform of PKC is located on the postsynaptic component of the neuromuscular junction but is also expressed by motoneurons in the spinal cord and in the motor nerve terminals. The results allow us to hypothesize that a spatially specific and opposing action of PKCtheta and PKA may result in activity-dependent alterations to synaptic connectivity at both the nerve inputs and the postsynaptic nAChR clusters.
authors.affiliation: Unitat d'Histologia i Neurobiologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Sant Llorenç 21, 43201 Reus, Spain. mariaangel.lanuza@urv.cat
authors.forename: Maria A
authors.initials: MA
authors.lastname: Lanuza
authors.forename: Núria
authors.initials: N
authors.lastname: Besalduch
authors.forename: Carmen
authors.initials: C
authors.lastname: González
authors.forename: Manel M
authors.initials: MM
authors.lastname: Santafé
authors.forename: Neus
authors.initials: N
authors.lastname: Garcia
authors.forename: Marta
authors.initials: M
authors.lastname: Tomàs
authors.forename: Phillip G
authors.initials: PG
authors.lastname: Nelson
authors.forename: Josep
authors.initials: J
authors.lastname: Tomàs
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D007527:Isoenzymes / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000235:genetics*; D010766:Phosphorylation / Q000235:genetics; D011493:Protein Kinase C / Q000172:deficiency* / Q000235:genetics; D000074121:Protein Kinase C-theta; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D013570:Synaptic Membranes / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics
chemical_list: C552917:Chrnd protein, mouse; C502449:Chrne protein, mouse; D007527:Isoenzymes; D021122:Protein Subunits; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D017868:Cyclic AMP-Dependent Protein Kinases; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta