Bassoon controls synaptic vesicle pools via regulation of presynaptic phosphorylation and cAMP homeostasis
Bassoon controls synaptic vesicle pools via regulation of presynaptic phosphorylation and cAMP homeostasis
Abstract Neuronal presynaptic terminals contain hundreds of neurotransmitter-filled synaptic vesicles (SVs). The morphologically uniform SVs differ in their release competence segregating into functional pools that differentially contribute to neurotransmission. The presynaptic scaffold bassoon is required for neurotransmission, but the underlying molecular mechanisms are unknown. We report that glutamatergic synapses lacking bassoon featured a decreased SV release competence and increased resting pool of SV as observed by imaging of SV release in cultured neurons. Further analyses in vitro and in vivo revealed a dysregulation of CDK5/calcineurin and cAMP/PKA presynaptic signalling resulting in an aberrant phosphorylation of their downstream effectors synapsin 1 and SNAP25, which are well-known regulators of SV release competence. An acute pharmacological restoration of physiological CDK5 and cAMP/PKA activity fully normalised the SV pools in neurons lacking bassoon. Finally, we demonstrated that CDK5-dependent regulation of PDE4 activity controls SV release competence by interaction with cAMP/PKA signalling. These data reveal that bassoon organises SV pools via regulation of presynaptic phosphorylation and indicate an involvement of PDE4 in the control of neurotransmitter release.
Andres-Alonso Maria、Lazarevic Vesna、Gundelfinger Eckart D.、Plattner Florian、Guhathakurta Debarpan、Pina-Fernandez Eneko、Fejtova Anna、Montenegro-Venegas Carolina
RG Presynaptic Plasticity, Leibniz Institute for NeurobiologyRG Presynaptic Plasticity, Leibniz Institute for NeurobiologyDepartment of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology||Center for Behavioral Brain Sciences (CBBS)||Institute for Pharmacology and Toxicology, Medical Faculty, Otto-von Guericke UniversityNeuro-research, HoustonMolecular Psychiatry, Department of Psychiatry and Psychotherapy, University Hospital Erlangen, Friedrich-Alexander Universit?t Erlangen-N¨1rnbergRG Presynaptic Plasticity, Leibniz Institute for NeurobiologyMolecular Psychiatry, Department of Psychiatry and Psychotherapy, University Hospital Erlangen, Friedrich-Alexander Universit?t Erlangen-N¨1rnberg||RG Presynaptic Plasticity, Leibniz Institute for NeurobiologyDepartment of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology||Center for Behavioral Brain Sciences (CBBS)||Institute for Pharmacology and Toxicology, Medical Faculty, Otto-von Guericke University
分子生物学细胞生物学生理学
Andres-Alonso Maria,Lazarevic Vesna,Gundelfinger Eckart D.,Plattner Florian,Guhathakurta Debarpan,Pina-Fernandez Eneko,Fejtova Anna,Montenegro-Venegas Carolina.Bassoon controls synaptic vesicle pools via regulation of presynaptic phosphorylation and cAMP homeostasis[EB/OL].(2025-03-28)[2025-04-28].https://www.biorxiv.org/content/10.1101/2021.07.22.453360.点此复制
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