Author, as appears in the article.: Cilleros-Mañé V; Just-Borràs L; Tomàs M; Garcia N; Tomàs JM; Lanuza MA

Department: Ciències Mèdiques Bàsiques

URV's Author/s: Cilleros Mañé, Víctor / Garcia Sancho, Maria de les Neus / Just Borràs, Laia / Lanuza Escolano, María Angel / Tomás Ferré, José Maria / Tomas Marginet, Marta

Keywords: Synaptosome-associated protein Spontaneous acetylcholine-release Snap-25 Protein-kinase-c Pka Neurotransmitter release Neuromuscular junction Muscarinic receptors Modulate transmitter release Long-term potentiation High-affinity binding Gene-expression Catalytic subunit Adenylate-cyclase activity snap-25 pka muscarinic receptors

Abstract: © 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.

Thematic Areas: 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

licence for use: https://creativecommons.org/licenses/by/3.0/es/

ISSN: 08926638

Author's mail: victor.cilleros@urv.cat marta.tomas@urv.cat mariaangel.lanuza@urv.cat laia.just@urv.cat josepmaria.tomas@urv.cat victor.cilleros@urv.cat

Author identifier: 0000-0001-5690-9932 0000-0002-4151-1697 0000-0003-4795-4103 0000-0003-0473-3730 0000-0002-0406-0006 0000-0001-5690-9932

Record's date: 2023-09-23

Papper version: info:eu-repo/semantics/submittedVersion

Link to the original source: https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fj.201902113R

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Faseb Journal. 34 (4): 4934-4955

APA: Cilleros-Mañé V; Just-Borràs L; Tomàs M; Garcia N; Tomàs JM; Lanuza MA (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

Article's DOI: 10.1096/fj.201902113R

Entity: Universitat Rovira i Virgili

Journal publication year: 2020

Publication Type: Journal Publications