Autor según el artículo: Hurtado E; Cilleros V; Nadal L; Simó A; Obis T; Garcia N; Santafé M; Tomàs M; Halievski K; Jordan C; Lanuza M; Tomàs J

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 / Santafé Martínez, Manuel / SIMÓ OLLÉ, ANNA / Tomás Ferré, José Maria / Tomas Marginet, Marta

Palabras clave: Pkc Neurotransmission Neuromuscular junction Muscle contraction Bdnf-trkb signaling pkc neuromuscular junction muscle contraction bdnf-trkb signaling

Resumen: © 2017 Hurtado, Cilleros, Nadal, Simó, Obis, Garcia, Santafé, Tomàs, Halievski, Jordan, Lanuza and Tomàs. The neurotrophin brain-derived neurotrophic factor (BDNF) acts via tropomyosin-related kinase B receptor (TrkB) to regulate synapse maintenance and function in the neuromuscular system. The potentiation of acetylcholine (ACh) release by BDNF requires TrkB phosphorylation and Protein Kinase C (PKC) activation. BDNF is secreted in an activity-dependent manner but it is not known if pre- and/or postsynaptic activities enhance BDNF expression in vivo at the neuromuscular junction (NMJ). Here, we investigated whether nerve and muscle cell activities regulate presynaptic conventional PKC (cPKCα and βI) via BDNF/TrkB signaling to modulate synaptic strength at the NMJ. To differentiate the effects of presynaptic activity from that of muscle contraction, we stimulated the phrenic nerve of rat diaphragms (1 Hz, 30 min) with or without contraction (abolished by µ-conotoxin GIIIB). Then, we performed ELISA, Western blotting, qRT-PCR, immunofluorescence and electrophysiological techniques. We found that nerve-induced muscle contraction: (1) increases the levels of mature BDNF protein without affecting pro-BDNF protein or BDNF mRNA levels; (2) downregulates TrkB.T1 without affecting TrkB.FL or p75 neurotrophin receptor (p75) levels; (3) increases presynaptic cPKCα and cPKCβI protein level through TrkB signaling; and (4) enhances phosphorylation of cPKCα and cPKCβI. Furthermore, we demonstrate that cPKCβI, which is exclusively located in the motor nerve terminals, increases activity-induced acetylcholine release. Together, these results show that nerve-induced muscle contraction is a key regulator of BDNF/TrkB signaling pathway, retrogradely activating presynaptic cPKC isoforms (in particular cPKCβI) to modulate synaptic function. These results indicate that a decrease in neuromuscular activity, as occurs in several neuromuscular disorders, could affect the BDNF/TrkB/PKC pathway that links pre- and postsynaptic activity to maintain neuromuscular function.

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: victor.cilleros@urv.cat marta.tomas@urv.cat manuel.santafe@urv.cat mariaangel.lanuza@urv.cat josepmaria.tomas@urv.cat victor.cilleros@urv.cat

Identificador del autor: 0000-0001-5690-9932 0000-0002-4151-1697 0000-0002-5462-5108 0000-0003-4795-4103 0000-0002-0406-0006 0000-0001-5690-9932

Fecha de alta del registro: 2023-09-02

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

Enlace a la fuente original: https://www.frontiersin.org/articles/10.3389/fnmol.2017.00147/full

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

Referencia al articulo segun fuente origial: Frontiers In Molecular Neuroscience. 10 147-

Referencia de l'ítem segons les normes APA: Hurtado E; Cilleros V; Nadal L; Simó A; Obis T; Garcia N; Santafé M; Tomàs M; Halievski K; Jordan C; Lanuza M; Tomàs J (2017). Muscle contraction regulates bdnf/trkb signaling to modulate synaptic function through presynaptic cPKCα and cPKCβi. Frontiers In Molecular Neuroscience, 10(), 147-. DOI: 10.3389/fnmol.2017.00147

DOI del artículo: 10.3389/fnmol.2017.00147

Entidad: Universitat Rovira i Virgili

Año de publicación de la revista: 2017

Tipo de publicación: Journal Publications