Articles producció científica> Ciències Mèdiques Bàsiques

The M2 muscarinic receptor, in association to M1, regulates the neuromuscular PKA molecular dynamics

  • Dades identificatives

    Identificador: imarina:6112203
    Autors:
    Cilleros-Mane, VictorJust-Borras, LaiaTomas, MartaGarcia, NeusTomas, Josep MariaLanuza, Maria Angel
    Resum:
    © 2020 Federation of American Societies for Experimental Biology Muscarinic acetylcholine receptor 1 subtype (M1) and muscarinic acetylcholine receptor 2 subtype (M2) presynaptic muscarinic receptor subtypes increase and decrease, respectively, neurotransmitter release at neuromuscular junctions. M2 involves protein kinase A (PKA), although the muscarinic regulation to form and inactivate the PKA holoenzyme is unknown. Here, we show that M2 signaling inhibits PKA by downregulating Cβ subunit, upregulating RIIα/β and liberating RIβ and RIIα to the cytosol. This promotes PKA holoenzyme formation and reduces the phosphorylation of the transmitter release target synaptosome-associated protein 25 and the gene regulator cAMP response element binding. Instead, M1 signaling, which is downregulated by M2, opposes to M2 by recruiting R subunits to the membrane. The M1 and M2 reciprocal actions are performed through the anchoring protein A kinase anchor protein 150 as a common node. Interestingly, M2 modulation on protein expression needs M1 signaling. Altogether, these results describe the dynamics of PKA subunits upon M2 muscarinic signaling in basal and under presynaptic nerve activity, uncover a specific involvement of the M1 receptor and reveal the M1/M2 balance to activate PKA to regulate neurotransmission. This provides a molecular mechanism to the PKA holoenzyme formation and inactivation which could be general to other synapses and cellular models.
  • Altres:

    Autor segons l'article: Cilleros-Mane, Victor; Just-Borras, Laia; Tomas, Marta; Garcia, Neus; Tomas, Josep Maria; Lanuza, Maria Angel
    Departament: Ciències Mèdiques Bàsiques
    Autor/s de la URV: Cilleros Mañé, Víctor / Garcia Sancho, Maria de les Neus / Just Borràs, Laia / Lanuza Escolano, María Angel / Tomás Ferré, José Maria / Tomas Marginet, Marta
    Paraules clau: Synaptosome-associated protein Spontaneous acetylcholine-release Snap-25 Receptor, muscarinic m2 Receptor, muscarinic m1 Rats, sprague-dawley Rats Protein-kinase-c Pka Neurotransmitter release Neuromuscular junction Muscarinic receptors Modulate transmitter release Male Long-term potentiation Humans High-affinity binding Hek293 cells Gene-expression Female Catalytic subunit Animals Amp-activated protein kinases Adenylate-cyclase activity snap-25 pka muscarinic receptors
    Resum: © 2020 Federation of American Societies for Experimental Biology Muscarinic acetylcholine receptor 1 subtype (M1) and muscarinic acetylcholine receptor 2 subtype (M2) presynaptic muscarinic receptor subtypes increase and decrease, respectively, neurotransmitter release at neuromuscular junctions. M2 involves protein kinase A (PKA), although the muscarinic regulation to form and inactivate the PKA holoenzyme is unknown. Here, we show that M2 signaling inhibits PKA by downregulating Cβ subunit, upregulating RIIα/β and liberating RIβ and RIIα to the cytosol. This promotes PKA holoenzyme formation and reduces the phosphorylation of the transmitter release target synaptosome-associated protein 25 and the gene regulator cAMP response element binding. Instead, M1 signaling, which is downregulated by M2, opposes to M2 by recruiting R subunits to the membrane. The M1 and M2 reciprocal actions are performed through the anchoring protein A kinase anchor protein 150 as a common node. Interestingly, M2 modulation on protein expression needs M1 signaling. Altogether, these results describe the dynamics of PKA subunits upon M2 muscarinic signaling in basal and under presynaptic nerve activity, uncover a specific involvement of the M1 receptor and reveal the M1/M2 balance to activate PKA to regulate neurotransmission. This provides a molecular mechanism to the PKA holoenzyme formation and inactivation which could be general to other synapses and cellular models.
    Àrees temàtiques: Saúde coletiva Química Psicología Odontología Nutrição Molecular biology Medicine (miscellaneous) Medicina veterinaria Medicina iii Medicina ii Medicina i Interdisciplinar Genetics General medicine Farmacia Engenharias iv Engenharias ii Educação física Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciências agrárias i Ciência de alimentos Cell biology Biotecnología Biotechnology Biology Biodiversidade Biochemistry & molecular biology Biochemistry Astronomia / física
    Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 08926638
    Adreça de correu electrònic de l'autor: laia.just@urv.cat marta.tomas@urv.cat victor.cilleros@alumni.urv.cat josepmaria.tomas@urv.cat laia.just@urv.cat mariaangel.lanuza@urv.cat
    Identificador de l'autor: 0000-0003-0473-3730 0000-0002-4151-1697 0000-0001-5690-9932 0000-0002-0406-0006 0000-0003-0473-3730 0000-0003-4795-4103
    Data d'alta del registre: 2024-10-12
    Versió de l'article dipositat: info:eu-repo/semantics/submittedVersion
    Enllaç font original: https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fj.201902113R
    URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referència a l'article segons font original: Faseb Journal. 34 (4): 4934-4955
    Referència de l'ítem segons les normes APA: Cilleros-Mane, Victor; Just-Borras, Laia; Tomas, Marta; Garcia, Neus; Tomas, Josep Maria; Lanuza, Maria Angel (2020). The M2 muscarinic receptor, in association to M1, regulates the neuromuscular PKA molecular dynamics. Faseb Journal, 34(4), 4934-4955. DOI: 10.1096/fj.201902113R
    DOI de l'article: 10.1096/fj.201902113R
    Entitat: Universitat Rovira i Virgili
    Any de publicació de la revista: 2020
    Tipus de publicació: Journal Publications
  • Paraules clau:

    Biochemistry,Biochemistry & Molecular Biology,Biology,Biotechnology,Cell Biology,Genetics,Medicine (Miscellaneous),Molecular Biology
    Synaptosome-associated protein
    Spontaneous acetylcholine-release
    Snap-25
    Receptor, muscarinic m2
    Receptor, muscarinic m1
    Rats, sprague-dawley
    Rats
    Protein-kinase-c
    Pka
    Neurotransmitter release
    Neuromuscular junction
    Muscarinic receptors
    Modulate transmitter release
    Male
    Long-term potentiation
    Humans
    High-affinity binding
    Hek293 cells
    Gene-expression
    Female
    Catalytic subunit
    Animals
    Amp-activated protein kinases
    Adenylate-cyclase activity
    snap-25
    pka
    muscarinic receptors
    Saúde coletiva
    Química
    Psicología
    Odontología
    Nutrição
    Molecular biology
    Medicine (miscellaneous)
    Medicina veterinaria
    Medicina iii
    Medicina ii
    Medicina i
    Interdisciplinar
    Genetics
    General medicine
    Farmacia
    Engenharias iv
    Engenharias ii
    Educação física
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Ciências ambientais
    Ciências agrárias i
    Ciência de alimentos
    Cell biology
    Biotecnología
    Biotechnology
    Biology
    Biodiversidade
    Biochemistry & molecular biology
    Biochemistry
    Astronomia / física
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