Articles producció científica> Medicina i Cirurgia

Synaptic retrograde regulation of the PKA-induced SNAP-25 and Synapsin-1 phosphorylation

  • Identification data

    Identifier: imarina:9292318
    Authors:
    Polishchuk, AleksandraCilleros-Mane, VictorJust-Borras, LaiaBalanya-Segura, MartaVandellos Pont, GenisSilvera Simon, CarolinaTomas, MartaGarcia, NeusTomas, JosepLanuza, Maria A
    Abstract:
    Bidirectional communication between presynaptic and postsynaptic components contribute to the homeostasis of the synapse. In the neuromuscular synapse, the arrival of the nerve impulse at the presynaptic terminal triggers the molecular mechanisms associated with ACh release, which can be retrogradely regulated by the resulting muscle contraction. This retrograde regulation, however, has been poorly studied. At the neuromuscular junction (NMJ), protein kinase A (PKA) enhances neurotransmitter release, and the phosphorylation of the molecules of the release machinery including synaptosomal associated protein of 25 kDa (SNAP-25) and Synapsin-1 could be involved.Accordingly, to study the effect of synaptic retrograde regulation of the PKA subunits and its activity, we stimulated the rat phrenic nerve (1 Hz, 30 min) resulting or not in contraction (abolished by µ-conotoxin GIIIB). Changes in protein levels and phosphorylation were detected by western blotting and cytosol/membrane translocation by subcellular fractionation. Synapsin-1 was localized in the levator auris longus (LAL) muscle by immunohistochemistry.Here we show that synaptic PKA Cβ subunit regulated by RIIβ or RIIα subunits controls activity-dependent phosphorylation of SNAP-25 and Synapsin-1, respectively. Muscle contraction retrogradely downregulates presynaptic activity-induced pSynapsin-1 S9 while that enhances pSNAP-25 T138. Both actions could coordinately contribute to decreasing the neurotransmitter release at the NMJ.This provides a molecular mechanism of the bidirectional communication between nerve terminals and muscle cells to balance the accurate process of ACh release, which could be important to characterize molecules as a therapy for neuromuscular diseases in which neuromuscular crosstalk is impai
  • Others:

    Author, as appears in the article.: Polishchuk, Aleksandra; Cilleros-Mane, Victor; Just-Borras, Laia; Balanya-Segura, Marta; Vandellos Pont, Genis; Silvera Simon, Carolina; Tomas, Marta; Garcia, Neus; Tomas, Josep; Lanuza, Maria A
    Department: Medicina i Cirurgia
    URV's Author/s: Balanya Segura, Marta / Cilleros Mañé, Víctor / Garcia Sancho, Maria de les Neus / Just Borràs, Laia / Lanuza Escolano, María Angel / POLISHCHUK, ALEKSANDRA / Tarazona Vega, Eshek / Tomás Ferré, José Maria / Tomas Marginet, Marta / TOMÀS ROIG, JORDI
    Keywords: Synaptic activity Synapsins Synapsin-1 Synapse Snap-25 Rats Protein-kinase-a Pka subunits Phosphorylation Neurotransmitter agents Neurotransmission Neuromuscular junction Homeostasis Electrical stimulation Biological transport Animals Ach release synaptosome-associated protein synaptic activity synapsin-1 synapse snap-25 pka subunits nicotinic acetylcholine-receptor neurotransmitter release neurotransmission neuromuscular-junction modulate transmitter release long-term potentiation electrical stimulation differential phosphorylation dependent phosphorylation catalytic subunit ach release
    Abstract: Bidirectional communication between presynaptic and postsynaptic components contribute to the homeostasis of the synapse. In the neuromuscular synapse, the arrival of the nerve impulse at the presynaptic terminal triggers the molecular mechanisms associated with ACh release, which can be retrogradely regulated by the resulting muscle contraction. This retrograde regulation, however, has been poorly studied. At the neuromuscular junction (NMJ), protein kinase A (PKA) enhances neurotransmitter release, and the phosphorylation of the molecules of the release machinery including synaptosomal associated protein of 25 kDa (SNAP-25) and Synapsin-1 could be involved.Accordingly, to study the effect of synaptic retrograde regulation of the PKA subunits and its activity, we stimulated the rat phrenic nerve (1 Hz, 30 min) resulting or not in contraction (abolished by µ-conotoxin GIIIB). Changes in protein levels and phosphorylation were detected by western blotting and cytosol/membrane translocation by subcellular fractionation. Synapsin-1 was localized in the levator auris longus (LAL) muscle by immunohistochemistry.Here we show that synaptic PKA Cβ subunit regulated by RIIβ or RIIα subunits controls activity-dependent phosphorylation of SNAP-25 and Synapsin-1, respectively. Muscle contraction retrogradely downregulates presynaptic activity-induced pSynapsin-1 S9 while that enhances pSNAP-25 T138. Both actions could coordinately contribute to decreasing the neurotransmitter release at the NMJ.This provides a molecular mechanism of the bidirectional communication between nerve terminals and muscle cells to balance the accurate process of ACh release, which could be important to characterize molecules as a therapy for neuromuscular diseases in which neuromuscular crosstalk is impaired.© 2023. The Author(s).
    Thematic Areas: Molecular biology General medicine Ciências biológicas ii Cell biology Biochemistry & molecular biology Biochemistry
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    Author's mail: marta.balanya@urv.cat aleksandra.polishchuk@urv.cat laia.just@urv.cat marta.tomas@urv.cat 0 0 aleksandra.polishchuk@urv.cat marta.balanya@urv.cat victor.cilleros@alumni.urv.cat josepmaria.tomas@urv.cat laia.just@urv.cat mariaangel.lanuza@urv.cat
    Author identifier: 0000-0003-0983-4944 0000-0001-6445-1538 0000-0003-0473-3730 0000-0002-4151-1697 0000-0001-6445-1538 0000-0003-0983-4944 0000-0001-5690-9932 0000-0002-0406-0006 0000-0003-0473-3730 0000-0003-4795-4103
    Record's date: 2024-10-12
    Papper version: info:eu-repo/semantics/publishedVersion
    Link to the original source: https://cmbl.biomedcentral.com/articles/10.1186/s11658-023-00431-2
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Cellular & Molecular Biology Letters. 28 (1): 17-17
    APA: Polishchuk, Aleksandra; Cilleros-Mane, Victor; Just-Borras, Laia; Balanya-Segura, Marta; Vandellos Pont, Genis; Silvera Simon, Carolina; Tomas, Marta; (2023). Synaptic retrograde regulation of the PKA-induced SNAP-25 and Synapsin-1 phosphorylation. Cellular & Molecular Biology Letters, 28(1), 17-17. DOI: 10.1186/s11658-023-00431-2
    Article's DOI: 10.1186/s11658-023-00431-2
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2023
    Publication Type: Journal Publications
  • Keywords:

    Biochemistry,Biochemistry & Molecular Biology,Cell Biology,Molecular Biology
    Synaptic activity
    Synapsins
    Synapsin-1
    Synapse
    Snap-25
    Rats
    Protein-kinase-a
    Pka subunits
    Phosphorylation
    Neurotransmitter agents
    Neurotransmission
    Neuromuscular junction
    Homeostasis
    Electrical stimulation
    Biological transport
    Animals
    Ach release
    synaptosome-associated protein
    synaptic activity
    synapsin-1
    synapse
    snap-25
    pka subunits
    nicotinic acetylcholine-receptor
    neurotransmitter release
    neurotransmission
    neuromuscular-junction
    modulate transmitter release
    long-term potentiation
    electrical stimulation
    differential phosphorylation
    dependent phosphorylation
    catalytic subunit
    ach release
    Molecular biology
    General medicine
    Ciências biológicas ii
    Cell biology
    Biochemistry & molecular biology
    Biochemistry
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