Author, as appears in the article.: Garcia, Neus; Balana, Cori; Lanuza, Maria A; Tomas, Marta; Cilleros-Mane, Victor; Just-Borras, Laia; Tomas, Josep
Department: Ciències Mèdiques Bàsiques
e-ISSN: 2073-4409
URV's Author/s: Cilleros Mañé, Víctor / Garcia Sancho, Maria de les Neus / Just Borràs, Laia / Lanuza Escolano, María Angel / Tomás Ferré, José Maria / Tomas Marginet, Marta / Tomàs Porres, Josep
Keywords: Trkb receptors; Synapses; Signal transduction; Serine kinases; Receptors, purinergic p1; Receptors, muscarinic; Protein-kinase-c; Protein kinase c; Protein isoforms; Presynaptic muscarinic receptors; Postsynaptic maturation; Postnatal synapse elimination; Pkc; Pka; Phosphorylation; Nicotinic acetylcholine-receptor; Neurotransmitter release; Neuromuscular junction; Muscle, skeletal; Muscarinic acetylcholine receptors; Motor endplate; Motor end-plate; Modulate transmitter release; Mice, transgenic; Mice, inbred c57bl; Mice; Male; Isoenzymes; Functional elimination; Cyclic amp-dependent protein kinases; Cell differentiation; Calcium-channels; Axons; Animals; Adenosine receptors; Acetylcholine release; Acetylcholine; trkb receptors; pkc; pka; muscarinic acetylcholine receptors; motor end-plate; adenosine receptors; acetylcholine release
Abstract: Background: During neuromuscular junction (NMJ) development, synapses are produced in excess. By sensing the activity-dependent release of ACh, adenosine, and neurotrophins, presynaptic receptors prompt axonal competition and loss of the unnecessary axons. The receptor action is mediated by synergistic and antagonistic relations when they couple to downstream kinases (mainly protein kinases A and C (PKA and PKC)), which phosphorylate targets involved in axonal disconnection. Here, we directly investigated the involvement of PKA subunits and PKC isoforms in synapse elimination. Methods: Selective PKA and PKC peptide modulators were applied daily to the Levator auris longus (LAL) muscle surface of P5-P8 transgenic B6.Cg-Tg (Thy1-YFP) 16 Jrs/J (and also C57BL/6J) mice, and the number of axons and the postsynaptic receptor cluster morphology were evaluated in P9 NMJ. Results: PKA (PKA-I and PKA-II isozymes) acts at the pre- and postsynaptic sites to delay both axonal elimination and nAChR cluster differentiation, PKC activity promotes both axonal loss (a cPKC beta I and nPKC epsilon isoform action), and postsynaptic nAChR cluster maturation (a possible role for PKC theta). Moreover, PKC-induced changes in axon number indirectly influence postsynaptic maturation. Conclusions: PKC and PKA have opposed actions, which suggests that changes in the balance of these kinases may play a major role in the mechanism of developmental synapse elimination.
Thematic Areas: Medicine (miscellaneous); Cell biology; Biochemistry, genetics and molecular biology (miscellaneous); Biochemistry, genetics and molecular biology (all)
licence for use: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 20734409
Author's mail: laia.just@urv.cat; marta.tomas@urv.cat; josep.tomaspo@estudiants.urv.cat; victor.cilleros@alumni.urv.cat; josepmaria.tomas@urv.cat; laia.just@urv.cat; mariaangel.lanuza@urv.cat
Record's date: 2025-01-28
Journal volume: 8
Paper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://www.mdpi.com/2073-4409/8/11/1304
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Paper original source: Cells. 8 (11): E1304-
APA: Garcia, Neus; Balana, Cori; Lanuza, Maria A; Tomas, Marta; Cilleros-Mane, Victor; Just-Borras, Laia; Tomas, Josep (2019). Opposed Actions of PKA Isozymes (RI and RII) and PKC Isoforms (cPKC beta I and nPKC epsilon) in Neuromuscular Developmental Synapse Elimination. Cells, 8(11), E1304-. DOI: 10.3390/cells8111304
Article's DOI: 10.3390/cells8111304
Entity: Universitat Rovira i Virgili
Journal publication year: 2019
Publication Type: Journal Publications
Repositori URV