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