Articles producció científica> Ciències Mèdiques Bàsiques

Involvement of the Voltage-Gated Calcium Channels L- P/Q- and N-Types in Synapse Elimination During Neuromuscular Junction Development

  • Identification data

    Identifier: imarina:9261806
    Authors:
    Garcia, NeusHernandez, PabloLanuza, Maria ATomas, MartaCilleros-Mane, VictorJust-Borras, LaiaDuran-Vigara, MariaPolishchuk, AleksandraBalanya-Segura, MartaTomas, Josep
    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
  • Others:

    Author, as appears in the article.: Garcia, Neus; Hernandez, Pablo; Lanuza, Maria A; Tomas, Marta; Cilleros-Mane, Victor; Just-Borras, Laia; Duran-Vigara, Maria; Polishchuk, Aleksandra; Balanya-Segura, Marta; Tomas, Josep
    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 Synapses Signal transduction Protein-kinase-c Protein kinases Protein isoforms Postnatal synapse elimination Neuromuscular junction Motor endplate Mice Calcium channels Calcium Axons Axonal competition Animals 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: marta.balanya@urv.cat aleksandra.polishchuk@urv.cat laia.just@urv.cat marta.tomas@urv.cat aleksandra.polishchuk@urv.cat marta.balanya@urv.cat victor.cilleros@alumni.urv.cat josepmaria.tomas@urv.cat laia.just@urv.cat mariaangel.lanuza@urv.cat
    Author identifier: 0000-0003-0983-4944 0000-0001-6445-1538 0000-0003-0473-3730 0000-0002-4151-1697 0000-0001-6445-1538 0000-0003-0983-4944 0000-0001-5690-9932 0000-0002-0406-0006 0000-0003-0473-3730 0000-0003-4795-4103
    Record's date: 2024-10-12
    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: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Molecular Neurobiology. 59 (7): 4044-4064
    APA: Garcia, Neus; Hernandez, Pablo; Lanuza, Maria A; Tomas, Marta; Cilleros-Mane, Victor; Just-Borras, Laia; Duran-Vigara, Maria; Polishchuk, Aleksandra; (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
  • Keywords:

    Cellular and Molecular Neuroscience,Neurology,Neuroscience (Miscellaneous),Neurosciences
    Vgcc
    Synapses
    Signal transduction
    Protein-kinase-c
    Protein kinases
    Protein isoforms
    Postnatal synapse elimination
    Neuromuscular junction
    Motor endplate
    Mice
    Calcium channels
    Calcium
    Axons
    Axonal competition
    Animals
    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
    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
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