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

Keywords: Trkb receptors Serine kinases Protein-kinase-c Presynaptic muscarinic receptors Postsynaptic maturation Postnatal synapse elimination Pkc Pka Nicotinic acetylcholine-receptor Neurotransmitter release Muscarinic acetylcholine receptors Motor end-plate Modulate transmitter release Functional elimination Calcium-channels Adenosine receptors Acetylcholine release 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: victor.cilleros@urv.cat mariaangel.lanuza@urv.cat laia.just@urv.cat victor.cilleros@urv.cat

Author identifier: 0000-0001-5690-9932 0000-0003-4795-4103 0000-0003-0473-3730 0000-0001-5690-9932

Record's date: 2023-09-02

Journal volume: 8

Papper version: info:eu-repo/semantics/publishedVersion

Link to the original source: https://www.mdpi.com/2073-4409/8/11/1304

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Cells. 8 (11):

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), -. DOI: 10.3390/cells8111304

Article's DOI: 10.3390/cells8111304

Entity: Universitat Rovira i Virgili

Journal publication year: 2019

Publication Type: Journal Publications