Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2005-2-17
pubmed:abstractText
AMPA-type glutamate receptors play a key role in mediating postsynaptic responses of excitatory neurotransmitters. It is now well accepted that AMPA receptors are also present at the presynapse, where they are thought to modulate neurotransmitter release. However, the mechanisms through which they control synaptic vesicle traffic have remained elusive. We used cultured hippocampal neurons and growth cone particles prepared from fetal rat brain to investigate the functional role of presynaptic AMPA receptors. We show here that stimulation of presynaptic AMPA receptors induces activation of mitogen-activated protein kinase (MAPK) through a nonreceptor tyrosine kinase-dependent and Na+/Ca2+-independent mechanism. This pathway is activated predominantly in axonal growth cones compared with the somatodendritic compartment. After stimulation of presynaptic AMPA receptors, synapsin I is phosphorylated at MAPK-specific sites. These events are paralleled by a prominent increase in evoked synaptic vesicle recycling that is blocked by the specific MAPK inhibitor 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one. Similarly, in synaptosomes isolated from adult brain, AMPA stimulation induces MAPK activation and phosphorylation of synapsin I at MAPK-dependent sites and enhances significantly synaptic vesicle recycling. These results reveal a novel pathway for activation of presynaptic MAPK and suggest a role of this pathway in the regulation of short-term presynaptic plasticity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
16
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1654-63
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15716401-Animals, pubmed-meshheading:15716401-Cells, Cultured, pubmed-meshheading:15716401-Cytoskeleton, pubmed-meshheading:15716401-Enzyme Activation, pubmed-meshheading:15716401-Exocytosis, pubmed-meshheading:15716401-Growth Cones, pubmed-meshheading:15716401-Hippocampus, pubmed-meshheading:15716401-MAP Kinase Signaling System, pubmed-meshheading:15716401-Neuronal Plasticity, pubmed-meshheading:15716401-Neurons, pubmed-meshheading:15716401-Phosphorylation, pubmed-meshheading:15716401-Presynaptic Terminals, pubmed-meshheading:15716401-Protein Processing, Post-Translational, pubmed-meshheading:15716401-Rats, pubmed-meshheading:15716401-Receptors, AMPA, pubmed-meshheading:15716401-Receptors, Presynaptic, pubmed-meshheading:15716401-Subcellular Fractions, pubmed-meshheading:15716401-Synapsins, pubmed-meshheading:15716401-Synaptic Vesicles, pubmed-meshheading:15716401-Synaptosomes, pubmed-meshheading:15716401-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
pubmed:year
2005
pubmed:articleTitle
A novel pathway for presynaptic mitogen-activated kinase activation via AMPA receptors.
pubmed:affiliation
Department of Medical Pharmacology, Consiglio Nazionale delle Ricerche, Institute of Neuroscience, Cellular and Molecular Pharmacology, Center of Excellence on Neurodegenerative Diseases, University of Milan, 20129 Milan, Italy.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural