Neurotrophins stimulate phosphorylation of synapsin I by MAP kinase and regulate synapsin I-actin interactions.
The ability of neurotrophins to modulate the survival and differentiation of neuronal populations involves the Trk/MAP (mitogen-activated protein kinase) kinase signaling pathway. More recently, neurotrophins have also been shown to regulate synaptic transmission. The synapsins are a family of neuron-specific phosphoproteins that play a role in regulation of neurotransmitter release, in axonal elongation, and in formation and maintenance of synaptic contacts. We report here that synapsin I is a downstream effector for the neurotrophin/Trk/MAP kinase cascade. Using purified components, we show that MAP kinase stoichiometrically phosphorylated synapsin I at three sites (Ser-62, Ser-67, and Ser-549). Phosphorylation of these sites was detected in rat brain homogenates, in cultured cerebrocortical neurons, and in isolated presynaptic terminals. Brain-derived neurotrophic factor and nerve growth factor upregulated phosphorylation of synapsin I at MAP kinase-dependent sites in intact cerebrocortical neurons and PC12 cells, respectively, while KCl- induced depolarization of cultured neurons decreased the phosphorylation state at these sites. MAP kinase-dependent phosphorylation of synapsin I significantly reduced its ability to promote G-actin polymerization and to bundle actin filaments. The results suggest that MAP kinase-dependent phosphorylation of synapsin I may contribute to the modulation of synaptic plasticity by neurotrophins and by other signaling pathways that converge at the level of MAP kinase activation.
Jovanovic
J N
JN
Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021-6399, USA.
Benfenati
F
F
Siow
Y L
YL
Sihra
T S
TS
Sanghera
J S
JS
Pelech
S L
SL
Greengard
P
P
Czernik
A J
AJ
D000199:Actins / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009473:Neuronal Plasticity; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction; D016704:Synapsins / Q000737:chemistry / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D000199:Actins; D009414:Nerve Growth Factors; D016704:Synapsins; D017871:Calcium-Calmodulin-Dependent Protein Kinases