Articles producció científica> Ciències Mèdiques Bàsiques

Membrane receptor-induced changes of the protein kinases A and C activity may play a leading role in promoting developmental synapse elimination at the neuromuscular junction

  • Datos identificativos

    Identificador: imarina:5131736
    Handle: https://hdl.handle.net/20.500.11797/imarina5131736
    Autores:
    Tomas, Josep MGarcia, NeusLanuza, Maria ANadal, LauraTomas, MartaHurtado, EricaSimo, AnnaCilleros, Victor
    Resumen:
    Synapses that are overproduced during histogenesis in the nervous system are eventually lost and connectivity is refined. Membrane receptor signaling leads to activity-dependent mutual influence and competition between axons directly or with the involvement of the postsynaptic cell and the associated glial cell/s. Presynaptic muscarinic acetylcholine (ACh) receptors (subtypes mAChR; M1, M2 and M4), adenosine receptors (AR; A1 and A2A) and the tropomyosin-related kinase B receptor (TrkB), among others, all cooperate in synapse elimination. Between these receptors there are several synergistic, antagonic and modulatory relations that clearly affect synapse elimination. Metabotropic receptors converge in a limited repertoire of intracellular effector kinases, particularly serine protein kinases A and C (PKA and PKC), to phosphorylate protein targets and bring about structural and functional changes leading to axon loss. In most cells A1, M1 and TrkB operate mainly by stimulating PKC whereas A2A, M2 and M4 inhibit PKA. We hypothesize that a membrane receptor-induced shifting in the protein kinases A and C activity (inhibition of PKA and/or stimulation of PKC) in some nerve endings may play an important role in promoting developmental synapse elimination at the neuromuscular junction (NMJ). This hypothesis is supported by: (i) the tonic effect (shown by using selective inhibitors) of several membrane receptors that accelerates axon loss between postnatal days P5-P9; (ii) the synergistic, antagonic and modulatory effects (shown by paired inhibition) of the receptors on axonal loss; (iii) the fact that the coupling of these receptors activates/inhibits the intracellular serine kinases; and (iv) the increase of the PKA activity, the reduction of the PKC activity or, in most cas

  • Otros:

    Autor según el artículo: Tomas, Josep M; Garcia, Neus; Lanuza, Maria A; Nadal, Laura; Tomas, Marta; Hurtado, Erica; Simo, Anna; Cilleros, Victor
    Departamento: Ciències Mèdiques Bàsiques
    Autor/es de la URV: Cilleros Mañé, Víctor / Garcia Sancho, Maria de les Neus / Hurtado Caballero, Erica / Lanuza Escolano, María Angel / NADAL MAGRIÑÀ, LAURA / SIMÓ OLLÉ, ANNA / Tomás Ferré, José Maria / Tomas Marginet, Marta
    Palabras clave: Synapse elimination Postnatal synapse elimination Pkc Pka Neurotrophins Neuromuscular junction Muscarinic acetylcholine receptors Motor end-plate Development Adenosine receptors Acetylcholine release pkc pka neurotrophins muscarinic acetylcholine receptors motor end-plate adenosine receptors acetylcholine release
    Resumen: Synapses that are overproduced during histogenesis in the nervous system are eventually lost and connectivity is refined. Membrane receptor signaling leads to activity-dependent mutual influence and competition between axons directly or with the involvement of the postsynaptic cell and the associated glial cell/s. Presynaptic muscarinic acetylcholine (ACh) receptors (subtypes mAChR; M1, M2 and M4), adenosine receptors (AR; A1 and A2A) and the tropomyosin-related kinase B receptor (TrkB), among others, all cooperate in synapse elimination. Between these receptors there are several synergistic, antagonic and modulatory relations that clearly affect synapse elimination. Metabotropic receptors converge in a limited repertoire of intracellular effector kinases, particularly serine protein kinases A and C (PKA and PKC), to phosphorylate protein targets and bring about structural and functional changes leading to axon loss. In most cells A1, M1 and TrkB operate mainly by stimulating PKC whereas A2A, M2 and M4 inhibit PKA. We hypothesize that a membrane receptor-induced shifting in the protein kinases A and C activity (inhibition of PKA and/or stimulation of PKC) in some nerve endings may play an important role in promoting developmental synapse elimination at the neuromuscular junction (NMJ). This hypothesis is supported by: (i) the tonic effect (shown by using selective inhibitors) of several membrane receptors that accelerates axon loss between postnatal days P5-P9; (ii) the synergistic, antagonic and modulatory effects (shown by paired inhibition) of the receptors on axonal loss; (iii) the fact that the coupling of these receptors activates/inhibits the intracellular serine kinases; and (iv) the increase of the PKA activity, the reduction of the PKC activity or, in most cases, both situations simultaneously that presumably occurs in all the situations of singly and paired inhibition of the mAChR, AR and TrkB receptors. The use of transgenic animals and various combinations of selective and specific PKA and PKC inhibitors could help to elucidate the role of these kinases in synapse maturation.
    Áreas temáticas: Neurosciences Molecular biology Medicina ii Ciências biológicas ii Cellular and molecular neuroscience
    Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 16625099
    Direcció de correo del autor: marta.tomas@urv.cat erica.hurtado@urv.cat victor.cilleros@alumni.urv.cat josepmaria.tomas@urv.cat mariaangel.lanuza@urv.cat
    Identificador del autor: 0000-0002-4151-1697 0000-0001-5690-9932 0000-0002-0406-0006 0000-0003-4795-4103
    Fecha de alta del registro: 2024-10-12
    Versión del articulo depositado: info:eu-repo/semantics/publishedVersion
    Enlace a la fuente original: https://www.frontiersin.org/articles/10.3389/fnmol.2017.00255
    URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referencia al articulo segun fuente origial: Frontiers In Molecular Neuroscience. 10 (255): 255-
    Referencia de l'ítem segons les normes APA: Tomas, Josep M; Garcia, Neus; Lanuza, Maria A; Nadal, Laura; Tomas, Marta; Hurtado, Erica; Simo, Anna; Cilleros, Victor (2017). Membrane receptor-induced changes of the protein kinases A and C activity may play a leading role in promoting developmental synapse elimination at the neuromuscular junction. Frontiers In Molecular Neuroscience, 10(255), 255-. DOI: 10.3389/fnmol.2017.00255
    DOI del artículo: 10.3389/fnmol.2017.00255
    Entidad: Universitat Rovira i Virgili
    Año de publicación de la revista: 2017
    Tipo de publicación: Journal Publications

  • Palabras clave:

    Cellular and Molecular Neuroscience,Molecular Biology,Neurosciences
    Synapse elimination
    Postnatal synapse elimination
    Pkc
    Pka
    Neurotrophins
    Neuromuscular junction
    Muscarinic acetylcholine receptors
    Motor end-plate
    Development
    Adenosine receptors
    Acetylcholine release
    pkc
    pka
    neurotrophins
    muscarinic acetylcholine receptors
    motor end-plate
    adenosine receptors
    acetylcholine release
    Neurosciences
    Molecular biology
    Medicina ii
    Ciências biológicas ii
    Cellular and molecular neuroscience

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