Synapsins as mediators of BDNF-enhanced neurotransmitter release.
We examined enhancement of synaptic transmission by neurotrophins at the presynaptic level. In a synaptosomal preparation, brain-derived neurotrophic factor (BDNF) increased mitogen-activated protein (MAP) kinase-dependent synapsin I phosphorylation and acutely facilitated evoked glutamate release. PD98059, used to inhibit MAP kinase activity, markedly decreased synapsin I phosphorylation and concomitantly reduced neurotransmitter release. The stimulation of glutamate release by BDNF was strongly attenuated in mice lacking synapsin I and/or synapsin II. These results indicate a causal link of synapsin phosphorylation via BDNF, TrkB receptors and MAP kinase with downstream facilitation of neurotransmitter release.
Jovanovic
J N
JN
Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York 10021, USA.
Czernik
A J
AJ
Fienberg
A A
AA
Greengard
P
P
Sihra
T S
TS
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D018698:Glutamic Acid / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009474:Neurons / Q000201:enzymology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D016704:Synapsins / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology*; D013574:Synaptosomes / Q000201:enzymology
D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D005419:Flavonoids; D016704:Synapsins; D018698:Glutamic Acid; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one