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 / 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: josep.tomas@urv.cat laia.just@urv.cat marta.tomas@urv.cat josep.tomas@urv.cat victor.cilleros@alumni.urv.cat laia.just@urv.cat mariaangel.lanuza@urv.cat
Author identifier: 0000-0003-0473-3730 0000-0002-4151-1697 0000-0001-5690-9932 0000-0003-0473-3730 0000-0003-4795-4103
Record's date: 2024-10-12
Journal volume: 8
Papper version: info:eu-repo/semantics/publishedVersion
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper 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
Entity: Universitat Rovira i Virgili
Journal publication year: 2019
Publication Type: Journal Publications
Repositori URV