Involvement of the Voltage-Gated Calcium Channels L- P/Q- and N-Types in Synapse Elimination During Neuromuscular Junction Development.

Autor: Garcia N; Facultat de Medicina i Ciències de la Salut, Unitat d'Histologia i Neurobiologia (UHNEUROB), Universitat Rovira i Virgili, Sant Llorenç 21, 43201, Reus, Spain. mariadelesneus.garcia@urv.cat., Hernández P; Facultat de Medicina i Ciències de la Salut, Unitat d'Histologia i Neurobiologia (UHNEUROB), Universitat Rovira i Virgili, Sant Llorenç 21, 43201, Reus, Spain., Lanuza MA; Facultat de Medicina i Ciències de la Salut, Unitat d'Histologia i Neurobiologia (UHNEUROB), Universitat Rovira i Virgili, Sant Llorenç 21, 43201, Reus, Spain., Tomàs M; Facultat de Medicina i Ciències de la Salut, Unitat d'Histologia i Neurobiologia (UHNEUROB), Universitat Rovira i Virgili, Sant Llorenç 21, 43201, Reus, Spain., Cilleros-Mañé V; Facultat de Medicina i Ciències de la Salut, Unitat d'Histologia i Neurobiologia (UHNEUROB), Universitat Rovira i Virgili, Sant Llorenç 21, 43201, Reus, Spain., Just-Borràs L; Facultat de Medicina i Ciències de la Salut, Unitat d'Histologia i Neurobiologia (UHNEUROB), Universitat Rovira i Virgili, Sant Llorenç 21, 43201, Reus, Spain., Duran-Vigara M; Facultat de Medicina i Ciències de la Salut, Unitat d'Histologia i Neurobiologia (UHNEUROB), Universitat Rovira i Virgili, Sant Llorenç 21, 43201, Reus, Spain., Polishchuk A; Facultat de Medicina i Ciències de la Salut, Unitat d'Histologia i Neurobiologia (UHNEUROB), Universitat Rovira i Virgili, Sant Llorenç 21, 43201, Reus, Spain., Balanyà-Segura M; Facultat de Medicina i Ciències de la Salut, Unitat d'Histologia i Neurobiologia (UHNEUROB), Universitat Rovira i Virgili, Sant Llorenç 21, 43201, Reus, Spain., Tomàs J; Facultat de Medicina i Ciències de la Salut, Unitat d'Histologia i Neurobiologia (UHNEUROB), Universitat Rovira i Virgili, Sant Llorenç 21, 43201, Reus, Spain. josepmaria.tomas@urv.cat.
Jazyk: angličtina
Zdroj: Molecular neurobiology [Mol Neurobiol] 2022 Jul; Vol. 59 (7), pp. 4044-4064. Date of Electronic Publication: 2022 Apr 27.
DOI: 10.1007/s12035-022-02818-2
Abstrakt: During the nervous system development, synapses are initially overproduced. In the neuromuscular junction (NMJ) however, competition between several motor nerve terminals and the synapses they made ends with the maturation of only one axon. The competitive signaling between axons is mediated by the differential activity-dependent release of the neurotransmitter ACh, co-transmitters, and neurotrophic factors. A multiple metabotropic receptor-driven downstream balance between PKA and PKC isoforms modulates the phosphorylation of targets involved in transmitter release and nerve terminal stability. Previously, we observed in the weakest endings on the polyinnervated NMJ that M 1 mAChR receptors reduce ACh release through the PKC pathway coupled to an excess of Ca 2+ inflow through P/Q- N- and L-type voltage-gated calcium channels (VGCC). This signaling would contribute to the elimination of this nerve terminal. Here, we investigate the involvement of the P/Q-, N-, and L-subtype channels in transgenic B6.Cg-Tg (Thy1-YFP)16-Jrs/J mice during synapse elimination. Then, the axon number and postsynaptic receptor cluster morphologic maturation were evaluated. The results show that both L- and P/Q-type VGCC (but not the N-type) are equally involved in synapse elimination. Their normal function favors supernumerary axonal loss by jointly enhancing intracellular calcium [Ca 2+ ] i . The block of these VGCCs or [Ca2+]i  i sequestration results in the same delay of axonal loss as the cPKCβI and nPKCε isoform block or PKA activation. The specific block of the muscle cell's contraction with μ-conotoxin GIIIB also delays synapse maturation, and thus, a retrograde influence from the postsynaptic site regulating the presynaptic CaV1.3 may contribute to the synapse elimination.
(© 2022. The Author(s).)
Databáze: MEDLINE
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