QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, November 8, 2006, 26(45):11670-11681; doi:10.1523/JNEUROSCI.3321-06.2006

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Menegon, A. Articles by Valtorta, F. Search for Related Content PubMed PubMed Citation Articles by Menegon, A. Articles by Valtorta, F. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL POTASSIUM CHLORIDE

 Previous Article  |  Next Article 

Cellular/Molecular
Protein Kinase A-Mediated Synapsin I Phosphorylation Is a Central Modulator of Ca²⁺-Dependent Synaptic Activity

Andrea Menegon,¹ Dario Bonanomi,¹ Chiara Albertinazzi,¹ Francesco Lotti,^1,2 Giuliana Ferrari,^1,2 Hung-Teh Kao,³ Fabio Benfenati,⁴ Pietro Baldelli,⁴ and Flavia Valtorta^1,5

¹San Raffaele Scientific Institute and "Vita-Salute" University, 20132 Milan, Italy, ²Telethon Institute for Gene Therapy, 20132 Milan, Italy, ³Nathan Kline Institute for Psychiatric Research, Orangeburg, New York 12229, ⁴Department of Neuroscience, The Italian Institute of Technology Central Laboratories and Department of Experimental Medicine, Section of Physiology, University of Genova, 16126 Genova, Italy, and ⁵The Italian Institute of Technology, Research Unit of Molecular Neuroscience, 20132 Milan, Italy

Correspondence should be addressed to Flavia Valtorta, Department of Biological and Technological Research 3A3, San Raffaele Scientific Institute, via Olgettina 58, 20132 Milan, Italy. Email: valtorta.flavia{at}hsr.it

Protein kinase A (PKA) modulates several steps of synaptic transmission. However, the identification of the mediators of these effects is as yet incomplete. Synapsins are synaptic vesicle (SV)-associated phosphoproteins that represent the major presynaptic targets of PKA. We show that, in hippocampal neurons, cAMP-dependent pathways affect SV exocytosis and that this effect is primarily brought about through synapsin I phosphorylation. Phosphorylation by PKA, by promoting dissociation of synapsin I from SVs, enhances the rate of SV exocytosis on stimulation. This effect becomes relevant when neurons are challenged with sustained stimulation, because it appears to counteract synaptic depression and accelerate recovery from depression by fostering the supply of SVs from the reserve pool to the readily releasable pool. In contrast, synapsin phosphorylation appears to be dispensable for the effects of cAMP on the frequency and amplitude of spontaneous synaptic currents and on the amplitude of evoked synaptic currents. The modulation of depolarization-evoked SV exocytosis by PKA phosphorylation of synapsin I is primarily caused by calmodulin (CaM)-dependent activation of cAMP pathways rather than by direct activation of CaM kinases. These data define a hierarchical crosstalk between cAMP- and CaM-dependent cascades and point to synapsin as a major effector of PKA in the modulation of activity-dependent SV exocytosis.

Key words: knock-out mice; lentiviruses; neurotransmitter release; phosphorylation; synapse; trafficking

---

Received April 27, 2006; revised Sept. 27, 2006; accepted Sept. 28, 2006.

Correspondence should be addressed to Flavia Valtorta, Department of Biological and Technological Research 3A3, San Raffaele Scientific Institute, via Olgettina 58, 20132 Milan, Italy. Email: valtorta.flavia{at}hsr.it

This article has been cited by other articles:

				M. Chiappalone, S. Casagrande, M. Tedesco, F. Valtorta, P. Baldelli, S. Martinoia, and F. Benfenati Opposite Changes in Glutamatergic and GABAergic Transmission Underlie the Diffuse Hyperexcitability of Synapsin I-Deficient Cortical Networks Cereb Cortex, June 1, 2009; 19(6): 1422 - 1439. [Abstract] [Full Text] [PDF]

				A. Khoutorsky and M. E. Spira Activity-dependent calpain activation plays a critical role in synaptic facilitation and post-tetanic potentiation Learn. Mem., January 29, 2009; 16(2): 129 - 141. [Abstract] [Full Text] [PDF]

				M. K. Tallent, N. Varghis, Y. Skorobogatko, L. Hernandez-Cuebas, K. Whelan, D. J. Vocadlo, and K. Vosseller In Vivo Modulation of O-GlcNAc Levels Regulates Hippocampal Synaptic Plasticity through Interplay with Phosphorylation J. Biol. Chem., January 2, 2009; 284(1): 174 - 181. [Abstract] [Full Text] [PDF]

				A. Corradi, A. Zanardi, C. Giacomini, F. Onofri, F. Valtorta, M. Zoli, and F. Benfenati Synapsin-I- and synapsin-II-null mice display an increased age-dependent cognitive impairment J. Cell Sci., September 15, 2008; 121(18): 3042 - 3051. [Abstract] [Full Text] [PDF]

				I. Gekel and E. Neher Application of an Epac Activator Enhances Neurotransmitter Release at Excitatory Central Synapses J. Neurosci., August 6, 2008; 28(32): 7991 - 8002. [Abstract] [Full Text] [PDF]

				K. L. Moulder, X. Jiang, C. Chang, A. A. Taylor, A. M. Benz, A. C. Conti, L. J. Muglia, and S. Mennerick A Specific Role for Ca2+-Dependent Adenylyl Cyclases in Recovery from Adaptive Presynaptic Silencing J. Neurosci., May 14, 2008; 28(20): 5159 - 5168. [Abstract] [Full Text] [PDF]

				P. Baldelli, A. Fassio, F. Valtorta, and F. Benfenati Lack of Synapsin I Reduces the Readily Releasable Pool of Synaptic Vesicles at Central Inhibitory Synapses J. Neurosci., December 5, 2007; 27(49): 13520 - 13531. [Abstract] [Full Text] [PDF]

				D. Fioravante, R.-Y. Liu, A. K. Netek, L. J. Cleary, and J. H. Byrne Synapsin Regulates Basal Synaptic Strength, Synaptic Depression, and Serotonin-Induced Facilitation of Sensorimotor Synapses in Aplysia J Neurophysiol, December 1, 2007; 98(6): 3568 - 3580. [Abstract] [Full Text] [PDF]

				W. S. Woods, J. M. Boettcher, D. H. Zhou, K. D. Kloepper, K. L. Hartman, D. T. Ladror, Z. Qi, C. M. Rienstra, and J. M. George Conformation-specific Binding of {alpha}-Synuclein to Novel Protein Partners Detected by Phage Display and NMR Spectroscopy J. Biol. Chem., November 23, 2007; 282(47): 34555 - 34567. [Abstract] [Full Text] [PDF]

				T. Nie, C. B. McDonough, T. Huang, P. V. Nguyen, and T. Abel Genetic Disruption of Protein Kinase A Anchoring Reveals a Role for Compartmentalized Kinase Signaling in Theta-Burst Long-Term Potentiation and Spatial Memory J. Neurosci., September 19, 2007; 27(38): 10278 - 10288. [Abstract] [Full Text] [PDF]

				F. Fiumara, C. Milanese, A. Corradi, S. Giovedi, G. Leitinger, A. Menegon, P. G. Montarolo, F. Benfenati, and M. Ghirardi Phosphorylation of synapsin domain A is required for post-tetanic potentiation J. Cell Sci., September 15, 2007; 120(18): 3228 - 3237. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help