 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
The Journal of Neuroscience, March 9, 2005, 25(10):2658-2669; doi:10.1523/JNEUROSCI.4278-04.2005
Previous Article | Next Article
Cellular/Molecular
Structural Domains Involved in the Regulation of Transmitter Release by Synapsins
Sabine Hilfiker,1,3 Fabio Benfenati,1,2 Frédéric Doussau,3,4 Angus C. Nairn,1 Andrew J. Czernik,1 George J. Augustine,3,4 andPaul Greengard1 1Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York 10021, 2Department of Experimental Medicine, Section of Human Physiology, University of Genova, 3-16132 Genova, Italy, 3Marine Biological Laboratory, Woods Hole, Massachusetts 02543, and 4Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710
Synapsins are a family of neuron-specific phosphoproteins that regulate neurotransmitter release by associating with synaptic vesicles. Synapsins consist of a series of conserved and variable structural domains of unknown function. We performed a systematic structure-function analysis of the various domains of synapsin by assessing the actions of synapsin fragments on neurotransmitter release, presynaptic ultrastructure, and the biochemical interactions of synapsin. Injecting a peptide derived from domain A into the squid giant presynaptic terminal inhibited neurotransmitter release in a phosphorylation-dependent manner. This peptide had no effect on vesicle pool size, synaptic depression, or transmitter release kinetics. In contrast, a peptide fragment from domain C reduced the number of synaptic vesicles in the periphery of the active zone and increased the rate and extent of synaptic depression. This peptide also slowed the kinetics of neurotransmitter release without affecting the number of docked vesicles. The domain C peptide, as well as another peptide from domain E that is known to have identical effects on vesicle pool size and release kinetics, both specifically interfered with the binding of synapsins to actin but not with the binding of synapsins to synaptic vesicles. This suggests that both peptides interfere with release by preventing interactions of synapsins with actin. Thus, interactions of domains C and E with the actin cytoskeleton may allow synapsins to perform two roles in regulating release, whereas domain A has an actin-independent function that regulates transmitter release in a phosphorylation-sensitive manner.
Key words: synapsin; release; regulation; neurotransmitter; actin; cytoskeleton; depression
Received Oct 14, 2004; revised January 20, 2005; accepted January 21, 2005.
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]
D. Gitler, Q. Cheng, P. Greengard, and G. J. Augustine
Synapsin IIa Controls the Reserve Pool of Glutamatergic Synaptic Vesicles
J. Neurosci., October 22, 2008; 28(43): 10835 - 10843.
[Abstract] [Full Text] [PDF]
W. L. Coleman, C. A. Bill, F. Simsek-Duran, G. Lonart, D. Samigullin, and M. Bykhovskaia
Synapsin II and calcium regulate vesicle docking and the cross-talk between vesicle pools at the mouse motor terminals
J. Physiol., October 1, 2008; 586(19): 4649 - 4673.
[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]
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]
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]
Y. Humeau, F. Doussau, M. R. Popoff, F. Benfenati, and B. Poulain
Fast changes in the functional status of release sites during short-term plasticity: involvement of a frequency-dependent bypass of Rac at Aplysia synapses
J. Physiol., September 15, 2007; 583(3): 983 - 1004.
[Abstract] [Full Text] [PDF]
V. Jensen, S. I. Walaas, S. Hilfiker, A. Ruiz, and O. Hvalby
A delayed response enhancement during hippocampal presynaptic plasticity in mice
J. Physiol., August 15, 2007; 583(1): 129 - 143.
[Abstract] [Full Text] [PDF]
N. A. Addy, E. F. Fornasiero, T. R. Stevens, J. R. Taylor, and M. R. Picciotto
Role of Calcineurin in Nicotine-Mediated Locomotor Sensitization
J. Neurosci., August 8, 2007; 27(32): 8571 - 8580.
[Abstract] [Full Text] [PDF]
F. Onofri, M. Messa, V. Matafora, G. Bonanno, A. Corradi, A. Bachi, F. Valtorta, and F. Benfenati
Synapsin Phosphorylation by Src Tyrosine Kinase Enhances Src Activity in Synaptic Vesicles
J. Biol. Chem., May 25, 2007; 282(21): 15754 - 15767.
[Abstract] [Full Text] [PDF]
A. Alaedini, H. Okamoto, C. Briani, K. Wollenberg, H. A. Shill, K. O. Bushara, H. W. Sander, P. H. R. Green, M. Hallett, and N. Latov
Immune Cross-Reactivity in Celiac Disease: Anti-Gliadin Antibodies Bind to Neuronal Synapsin I
J. Immunol., May 15, 2007; 178(10): 6590 - 6595.
[Abstract] [Full Text] [PDF]
P. Nunes, N. Haines, V. Kuppuswamy, D. J. Fleet, and B. A. Stewart
Synaptic Vesicle Mobility and Presynaptic F-Actin Are Disrupted in a N-ethylmaleimide-sensitive Factor Allele of Drosophila
Mol. Biol. Cell, November 1, 2006; 17(11): 4709 - 4719.
[Abstract] [Full Text] [PDF]
A. Fassio, D. Merlo, J. Mapelli, A. Menegon, A. Corradi, M. Mete, S. Zappettini, G. Bonanno, F. Valtorta, E. D'Angelo, et al.
The synapsin domain E accelerates the exoendocytotic cycle of synaptic vesicles in cerebellar Purkinje cells
J. Cell Sci., October 15, 2006; 119(20): 4257 - 4268.
[Abstract] [Full Text] [PDF]
S. V. Yelamanchili, G. Pendyala, I. Brunk, M. Darna, U. Albrecht, and G. Ahnert-Hilger
Differential Sorting of the Vesicular Glutamate Transporter 1 into a Defined Vesicular Pool Is Regulated by Light Signaling Involving the Clock Gene Period2
J. Biol. Chem., June 9, 2006; 281(23): 15671 - 15679.
[Abstract] [Full Text] [PDF]
A. Kielland, A. Erisir, S. I. Walaas, and P. Heggelund
Synapsin Utilization Differs among Functional Classes of Synapses on Thalamocortical Cells
J. Neurosci., May 24, 2006; 26(21): 5786 - 5793.
[Abstract] [Full Text] [PDF]
O. Hvalby, V. Jensen, H.-T. Kao, and S. I. Walaas
Synapsin-regulated synaptic transmission from readily releasable synaptic vesicles in excitatory hippocampal synapses in mice
J. Physiol., February 15, 2006; 571(1): 75 - 82.
[Abstract] [Full Text] [PDF]
R. McMullan, E. Hiley, P. Morrison, and S. J. Nurrish
Rho is a presynaptic activator of neurotransmitter release at pre-existing synapses in C. elegans
Genes & Dev., January 1, 2006; 20(1): 65 - 76.
[Abstract] [Full Text] [PDF]
H. Photowala, R. Freed, and S. Alford
Location and function of vesicle clusters, active zones and Ca2+ channels in the lamprey presynaptic terminal
J. Physiol., November 15, 2005; 569(1): 119 - 135.
[Abstract] [Full Text] [PDF]
M. Y Lin, H. Teng, and R. S Wilkinson
Vesicles in snake motor terminals comprise one functional pool and utilize a single recycling strategy at all stimulus frequencies
J. Physiol., October 15, 2005; 568(2): 413 - 421.
[Abstract] [Full Text] [PDF]
B. Michels, S. Diegelmann, H. Tanimoto, I. Schwenkert, E. Buchner, and B. Gerber
A role for Synapsin in associative learning: The Drosophila larva as a study case
Learn. Mem., May 1, 2005; 12(3): 224 - 231.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|