title: Kainate induces mobilization of synaptic vesicles at the growth cone through the activation of protein kinase A.
abstract: Activation of protein kinase A (PKA) pathway at presynaptic terminals plays a crucial role in the supply of synaptic vesicles (SVs) from the reserve pool, affecting the steady-state level of activity and the reconstitution of the readily releasable pool after intense stimulation. However, the identity of the stimuli activating this pathway is undefined. Using fluorescence resonance energy transfer and molecular genetic, we show that kainate, through the activation of presynaptic kainate receptors, induces PKA activation and enhances synapsin I phosphorylation at PKA-specific residues. This leads to a dispersion of synapsin I immunoreactivity, which is accompanied by a PKA-dependent increase in the rate of SV recycling at the growth cone and by an enhanced miniature excitatory postsynaptic currents frequency in mature networks. Selective activation of this pathway is induced by the native neurotransmitter glutamate, when applied in the high nanomolar range. These data identify glutamate, specifically acting on KARs, as one of the stimuli able to induce phosphorylation of synapsin at PKA sites, both at the axonal growth cone and at the mature synapse, thus increasing SV availability and contributing to plasticity phenomena.
authors.affiliation: Department of Medical Pharmacology and Consiglio Nazionale delle Ricerche (CNR) Institute of Neuroscience, University of Milano, 20129 Milano, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Gelsomino
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Menna
authors.forename: Flavia
authors.initials: F
authors.lastname: Antonucci
authors.forename: Simona
authors.initials: S
authors.lastname: Rodighiero
authors.forename: Loredana
authors.initials: L
authors.lastname: Riganti
authors.forename: Christophe
authors.initials: C
authors.lastname: Mulle
authors.forename: Fabio
authors.initials: F
authors.lastname: Benfenati
authors.forename: Flavia
authors.initials: F
authors.lastname: Valtorta
authors.forename: Claudia
authors.initials: C
authors.lastname: Verderio
authors.forename: Michela
authors.initials: M
authors.lastname: Matteoli
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000378:metabolism / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D031541:Fluorescence Resonance Energy Transfer; D018698:Glutamic Acid / Q000378:metabolism; D020439:Growth Cones / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000378:metabolism / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D018408:Patch-Clamp Techniques; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D018092:Kainic Acid Receptors / Q000378:metabolism*; D016704:Synapsins / Q000378:metabolism; D013572:Synaptic Vesicles / Q000502:physiology*
chemical_list: D017868:Cyclic AMP-Dependent Protein Kinases; D018690:Excitatory Amino Acid Agonists; D018698:Glutamic Acid; D007608:Kainic Acid; D034741:RNA, Small Interfering; D018092:Kainic Acid Receptors; D016704:Synapsins