Author, as appears in the article.: Garcia N; Hernández P; Lanuza MA; Tomàs M; Cilleros-Mañé V; Just-Borràs L; Duran-Vigara M; Polishchuk A; Balanyà-Segura M; Tomàs J
Department: Ciències Mèdiques Bàsiques
URV's Author/s: Balanya Segura, Marta / Cilleros Mañé, Víctor / Garcia Sancho, Maria de les Neus / Just Borràs, Laia / Lanuza Escolano, María Angel / POLISHCHUK, ALEKSANDRA / Tomás Ferré, José Maria / Tomas Marginet, Marta
Keywords: Vgcc Protein-kinase-c Protein kinases Postnatal synapse elimination Motor endplate Axonal competition weak inputs vgcc transmitter release skeletal-muscle receptors protein kinases postnatal synapse elimination neurotransmitter release muscarinic autoreceptors ca2+ channel axonal competition adenosine a(2a) acetylcholine-release
Abstract: During the nervous system development, synapses are initially overproduced. In the neuromuscular junction (NMJ) however, competition between several motor nerve terminals and the synapses they made ends with the maturation of only one axon. The competitive signaling between axons is mediated by the differential activity-dependent release of the neurotransmitter ACh, co-transmitters, and neurotrophic factors. A multiple metabotropic receptor-driven downstream balance between PKA and PKC isoforms modulates the phosphorylation of targets involved in transmitter release and nerve terminal stability. Previously, we observed in the weakest endings on the polyinnervated NMJ that M1 mAChR receptors reduce ACh release through the PKC pathway coupled to an excess of Ca2+ inflow through P/Q- N- and L-type voltage-gated calcium channels (VGCC). This signaling would contribute to the elimination of this nerve terminal. Here, we investigate the involvement of the P/Q-, N-, and L-subtype channels in transgenic B6.Cg-Tg (Thy1-YFP)16-Jrs/J mice during synapse elimination. Then, the axon number and postsynaptic receptor cluster morphologic maturation were evaluated. The results show that both L- and P/Q-type VGCC (but not the N-type) are equally involved in synapse elimination. Their normal function favors supernumerary axonal loss by jointly enhancing intracellular calcium [Ca2+]i. The block of these VGCCs or [Ca2+]i i sequestration results in the same delay of axonal loss as the cPKCβI and nPKCε isoform block or PKA activation. The specific block of the muscle cell's contraction with μ-conotoxin GIIIB also delays synapse maturation, and thus, a retrograde influence from the postsynaptic site regulating the presynaptic CaV1.3 may contribute to the synapse elimination.© 2022. The Author(s).
Thematic Areas: Saúde coletiva Química Odontología Nutrição Neurosciences Neuroscience (miscellaneous) Neurology Medicina veterinaria Medicina iii Medicina ii Medicina i Materiais Interdisciplinar Farmacia Ensino Engenharias iv Engenharias ii Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Cellular and molecular neuroscience Biotecnología Biodiversidade Administração pública e de empresas, ciências contábeis e turismo
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: victor.cilleros@urv.cat marta.balanya@urv.cat marta.tomas@urv.cat aleksandra.polishchuk@urv.cat mariaangel.lanuza@urv.cat laia.just@urv.cat josepmaria.tomas@urv.cat victor.cilleros@urv.cat marta.balanya@urv.cat aleksandra.polishchuk@urv.cat
Author identifier: 0000-0001-5690-9932 0000-0003-0983-4944 0000-0002-4151-1697 0000-0001-6445-1538 0000-0003-4795-4103 0000-0003-0473-3730 0000-0002-0406-0006 0000-0001-5690-9932 0000-0003-0983-4944 0000-0001-6445-1538
Record's date: 2023-09-02
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://link.springer.com/article/10.1007/s12035-022-02818-2
Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Molecular Neurobiology. 59 (7): 4044-4064
APA: Garcia N; Hernández P; Lanuza MA; Tomàs M; Cilleros-Mañé V; Just-Borràs L; Duran-Vigara M; Polishchuk A; Balanyà-Segura M; Tomàs J (2022). Involvement of the Voltage-Gated Calcium Channels L- P/Q- and N-Types in Synapse Elimination During Neuromuscular Junction Development. Molecular Neurobiology, 59(7), 4044-4064. DOI: 10.1007/s12035-022-02818-2
Article's DOI: 10.1007/s12035-022-02818-2
Entity: Universitat Rovira i Virgili
Journal publication year: 2022
Publication Type: Journal Publications
Repositori URV