MAPK/Erk-dependent phosphorylation of synapsin mediates formation of functional synapses and short-term homosynaptic plasticity.

Publisher: Company of Biologists Country of Publication: England NLM ID: 0052457 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1477-9137 (Electronic) Linking ISSN: 00219533 NLM ISO Abbreviation: J Cell Sci Subsets: MEDLINE

Publication: Cambridge : Company of Biologists
Original Publication: London.

Extracellular Signal-Regulated MAP Kinases/*metabolism ; Helix, Snails/*enzymology ; Neuronal Plasticity/*physiology ; Synapses/*enzymology ; Synapsins/*metabolism; Amino Acid Sequence ; Animals ; Butadienes/pharmacology ; Cells, Cultured ; Cluster Analysis ; Conserved Sequence ; Enzyme Activation/drug effects ; Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors ; Helix, Snails/drug effects ; Long-Term Potentiation/drug effects ; Molecular Sequence Data ; Neuronal Plasticity/drug effects ; Neurons/drug effects ; Neurons/enzymology ; Nitriles/pharmacology ; Phosphorylation/drug effects ; Phylogeny ; Presynaptic Terminals/drug effects ; Presynaptic Terminals/enzymology ; Protein Kinase Inhibitors/pharmacology ; Protein Structure, Tertiary ; Substrate Specificity/drug effects ; Synapses/drug effects ; Synapsins/chemistry ; Time Factors

MAPK/Erk is a protein kinase activated by neurotrophic factors involved in synapse formation and plasticity, which acts at both the nuclear and cytoplasmic level. Synapsin proteins are synaptic-vesicle-associated proteins that are well known to be MAPK/Erk substrates at phylogenetically conserved sites. However, the physiological role of MAPK/Erk-dependent synapsin phosphorylation in regulating synaptic formation and function is poorly understood. Here, we examined whether synapsin acts as a physiological effector of MAPK/Erk in synaptogenesis and plasticity. To this aim, we developed an in vitro model of soma-to-soma paired Helix B2 neurons, that establish bidirectional excitatory synapses. We found that the formation and activity-dependent short-term plasticity of these synapses is dependent on the MAPK/Erk pathway. To address the role of synapsin in this pathway, we generated non-phosphorylatable and pseudo-phosphorylated Helix synapsin mutants at the MAPK/Erk sites. Overexpression experiments revealed that both mutants interfere with presynaptic differentiation, synapsin clustering, and severely impair post-tetanic potentiation, a form of short-term homosynaptic plasticity. Our findings show that MAPK/Erk-dependent synapsin phosphorylation has a dual role both in the establishment of functional synaptic connections and their short-term plasticity, indicating that some of the multiple extranuclear functions of MAPK/Erk in neurons can be mediated by the same multifunctional presynaptic target.

GGP09134 Italy TI_ Telethon

0 (Butadienes)
0 (Nitriles)
0 (Protein Kinase Inhibitors)
0 (Synapsins)
0 (U 0126)
EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)

Date Created: 20100218 Date Completed: 20100615 Latest Revision: 20211020

20231215

10.1242/jcs.056846

20159961