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- Title
Phosphorylation of Synapsin I by Cyclin-Dependent Kinase- 5 Sets the Ratio between the Resting and Recycling Pools of Synaptic Vesicles at Hippocampal Synapses.
- Authors
Verstegen, Anne M. J.; Tagliatti, Erica; Lignani, Gabriele; Marte, Antonella; Stolero, Tamar; Atias, Merav; Corradi, Anna; Valtorta, Flavia; Gitler, Daniel; Onofri, Franco; Fassio, Anna; Benfenati, Fabio
- Abstract
Cyclin-dependentkinase-5(Cdk5)wasreported todownscaleneurotransmissionbysequestering synaptic vesicles(SVs)in the release-reluctant resting pool, but the molecular targets mediating this activity remain unknown. Synapsin I (SynI), a major SV phosphoprotein involved in the regulation ofSVtrafficking and neurotransmitter release, is one of the presynaptic substrates of Cdk5, which phosphorylates it in its C-terminal region at Ser549 (site 6)andSer551 (site 7).Herewedemonstrate thatCdk5phosphorylation of SynI fine tunes the recruitment of SVsto the active recycling pool and contributes to the Cdk5-mediated homeostatic responses. Phosphorylation of SynI by Cdk5 is physiologically regulated and enhancesits binding to F-actin. The effects ofCdk5inhibitiononthe sizeanddepletion kinetics of the recycling pool, as well asonSVdistribution within the nerve terminal, are virtually abolished in mouse SynI knock-out (KO) neurons or in KO neurons expressing the dephosphomimetic SynI mutants at sites 6,7 or site 7 only. The observation that the single site-7 mutant phenocopies the effects of the deletion of SynI identifies this site as the central switch in mediating the synaptic effects ofCdk5anddemonstrates that SynI is necessaryandsufficient for achieving the effects of the kinase on SV trafficking. The phosphorylation state of SynI by Cdk5 at site 7 is regulated during chronic modification of neuronal activity and is an essential downstream effector for the Cdk5-mediated homeostatic scaling.
- Subjects
PHOSPHORYLATION; SYNAPSINS; CYCLIN-dependent kinases; SYNAPTIC vesicles; NERVE endings; HIPPOCAMPUS (Brain); PHOSPHOPROTEINS
- Publication
Journal of Neuroscience, 2014, Vol 34, Issue 21, p7266
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.3973-13.2014