Autor según el artículo: Cilleros-Mañé V; Just-Borràs L; Polishchuk A; Durán M; Tomàs M; Garcia N; Tomàs JM; Lanuza MA

Departamento: Ciències Mèdiques Bàsiques

Autor/es de la URV: 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

Palabras clave: Snap-25 Protein-kinase-c Pkc Pdk1 Neuromuscular junction Muscarinic receptors transmitter release synaptosome-associated protein synaptic activity snap-25 possible involvement pkc pdk1 neurotransmitter release neuromuscular-junction neuromuscular junction muscarinic autoreceptors epidermal-growth-factor dependent phosphorylation

Resumen: Neuromuscular junctions (NMJ) regulate cholinergic exocytosis through the M1 and M2 muscarinic acetylcholine autoreceptors (mAChR), involving the crosstalk between receptors and downstream pathways. Protein kinase C (PKC) regulates neurotransmission but how it associates with the mAChRs remains unknown. Here, we investigate whether mAChRs recruit the classical PKCβI and the novel PKCε isoforms and modulate their priming by PDK1, translocation and activity on neurosecretion targets. We show that each M1 and M2 mAChR activates the master kinase PDK1 and promotes a particular priming of the presynaptic PKCβI and ε isoforms. M1 recruits both primed-PKCs to the membrane and promotes Munc18-1, SNAP-25, and MARCKS phosphorylation. In contrast, M2 downregulates PKCε through a PKA-dependent pathway, which inhibits Munc18-1 synthesis and PKC phosphorylation. In summary, our results discover a co-dependent balance between muscarinic autoreceptors which orchestrates the presynaptic PKC and their action on ACh release SNARE-SM mechanism. Altogether, this molecular signaling explains previous functional studies at the NMJ and guide toward potential therapeutic targets.

Áreas temáticas: 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

Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/

Direcció de correo del autor: victor.cilleros@urv.cat marta.tomas@urv.cat aleksandra.polishchuk@urv.cat mariaangel.lanuza@urv.cat laia.just@urv.cat josepmaria.tomas@urv.cat victor.cilleros@urv.cat aleksandra.polishchuk@urv.cat

Identificador del autor: 0000-0001-5690-9932 0000-0002-4151-1697 0000-0001-6445-1538 0000-0003-4795-4103 0000-0003-0473-3730 0000-0002-0406-0006 0000-0001-5690-9932 0000-0001-6445-1538

Fecha de alta del registro: 2023-09-02

Volumen de revista: 35

Versión del articulo depositado: info:eu-repo/semantics/publishedVersion

Enlace a la fuente original: https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202002213R

URL Documento de licencia: http://repositori.urv.cat/ca/proteccio-de-dades/

Referencia al articulo segun fuente origial: Faseb Journal. 35 (7): e21724-

Referencia de l'ítem segons les normes APA: Cilleros-Mañé V; Just-Borràs L; Polishchuk A; Durán M; Tomàs M; Garcia N; Tomàs JM; Lanuza MA (2021). M1 and M2 mAChRs activate PDK1 and regulate PKC βI and ε and the exocytotic apparatus at the NMJ. Faseb Journal, 35(7), e21724-. DOI: 10.1096/fj.202002213R

DOI del artículo: 10.1096/fj.202002213R

Entidad: Universitat Rovira i Virgili

Año de publicación de la revista: 2021

Tipo de publicación: Journal Publications