Abstract
Synapsin I is a neuron-specific phosphoprotein that binds to small synaptic vesicles and actin filaments in a phosphorylation-dependent fashion. It has been hypothesized that dephosphorylated synapsin I inhibits neurotransmitter release either by forming a cage around synaptic vesicles (cage model) or by anchoring them to the F-actin cytoskeleton of the nerve terminal (crosslinking model). Computer modeling was performed with the aim of testing the impact of phosphorylation on the molecular interactions of synapsin I within the nerve terminal. The results of the simulation experiments demonstrate that in the crosslinking model the phosphorylation of synapsin I causes a severalfold increase in the number of vesicles released from the cytoskeleton and that in the cage model the phosphorylation induces a 2-fold increase in the number of vesicles bearing one or more unsaturated synapsin I binding sites. These data are compatible with the view that the function of synapsin I in the short-term regulation of neurotransmitter release is to induce a phosphorylation-dependent transition of synaptic vesicles from a "reserve pool" to a readily "releasable pool" of vesicles.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- BOYD I. A., MARTIN A. R. The end-plate potential in mammalian muscle. J Physiol. 1956 Apr 27;132(1):74–91. doi: 10.1113/jphysiol.1956.sp005503. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Benfenati F., Bähler M., Jahn R., Greengard P. Interactions of synapsin I with small synaptic vesicles: distinct sites in synapsin I bind to vesicle phospholipids and vesicle proteins. J Cell Biol. 1989 May;108(5):1863–1872. doi: 10.1083/jcb.108.5.1863. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Benfenati F., Greengard P., Brunner J., Bähler M. Electrostatic and hydrophobic interactions of synapsin I and synapsin I fragments with phospholipid bilayers. J Cell Biol. 1989 May;108(5):1851–1862. doi: 10.1083/jcb.108.5.1851. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bähler M., Benfenati F., Valtorta F., Czernik A. J., Greengard P. Characterization of synapsin I fragments produced by cysteine-specific cleavage: a study of their interactions with F-actin. J Cell Biol. 1989 May;108(5):1841–1849. doi: 10.1083/jcb.108.5.1841. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bähler M., Greengard P. Synapsin I bundles F-actin in a phosphorylation-dependent manner. Nature. 1987 Apr 16;326(6114):704–707. doi: 10.1038/326704a0. [DOI] [PubMed] [Google Scholar]
- Ceccarelli B., Hurlbut W. P. Vesicle hypothesis of the release of quanta of acetylcholine. Physiol Rev. 1980 Apr;60(2):396–441. doi: 10.1152/physrev.1980.60.2.396. [DOI] [PubMed] [Google Scholar]
- DEL CASTILLO J., KATZ B. Quantal components of the end-plate potential. J Physiol. 1954 Jun 28;124(3):560–573. doi: 10.1113/jphysiol.1954.sp005129. [DOI] [PMC free article] [PubMed] [Google Scholar]
- De Camilli P., Benfenati F., Valtorta F., Greengard P. The synapsins. Annu Rev Cell Biol. 1990;6:433–460. doi: 10.1146/annurev.cb.06.110190.002245. [DOI] [PubMed] [Google Scholar]
- De Camilli P., Harris S. M., Jr, Huttner W. B., Greengard P. Synapsin I (Protein I), a nerve terminal-specific phosphoprotein. II. Its specific association with synaptic vesicles demonstrated by immunocytochemistry in agarose-embedded synaptosomes. J Cell Biol. 1983 May;96(5):1355–1373. doi: 10.1083/jcb.96.5.1355. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Elmqvist D., Quastel D. M. A quantitative study of end-plate potentials in isolated human muscle. J Physiol. 1965 Jun;178(3):505–529. doi: 10.1113/jphysiol.1965.sp007639. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Forn J., Greengard P. Depolarizing agents and cyclic nucleotides regulate the phosphorylation of specific neuronal proteins in rat cerebral cortex slices. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5195–5199. doi: 10.1073/pnas.75.10.5195. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hackett J. T., Cochran S. L., Greenfield L. J., Jr, Brosius D. C., Ueda T. Synapsin I injected presynaptically into goldfish mauthner axons reduces quantal synaptic transmission. J Neurophysiol. 1990 Apr;63(4):701–706. doi: 10.1152/jn.1990.63.4.701. [DOI] [PubMed] [Google Scholar]
- Huttner W. B., Schiebler W., Greengard P., De Camilli P. Synapsin I (protein I), a nerve terminal-specific phosphoprotein. III. Its association with synaptic vesicles studied in a highly purified synaptic vesicle preparation. J Cell Biol. 1983 May;96(5):1374–1388. doi: 10.1083/jcb.96.5.1374. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jahn R., Schiebler W., Greengard P. A quantitative dot-immunobinding assay for proteins using nitrocellulose membrane filters. Proc Natl Acad Sci U S A. 1984 Mar;81(6):1684–1687. doi: 10.1073/pnas.81.6.1684. [DOI] [PMC free article] [PubMed] [Google Scholar]
- KATZ B., MILEDI R. THE EFFECT OF CALCIUM ON ACETYLCHOLINE RELEASE FROM MOTOR NERVE TERMINALS. Proc R Soc Lond B Biol Sci. 1965 Feb 16;161:496–503. doi: 10.1098/rspb.1965.0017. [DOI] [PubMed] [Google Scholar]
- Lin J. W., Sugimori M., Llinás R. R., McGuinness T. L., Greengard P. Effects of synapsin I and calcium/calmodulin-dependent protein kinase II on spontaneous neurotransmitter release in the squid giant synapse. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8257–8261. doi: 10.1073/pnas.87.21.8257. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Llinás R., McGuinness T. L., Leonard C. S., Sugimori M., Greengard P. Intraterminal injection of synapsin I or calcium/calmodulin-dependent protein kinase II alters neurotransmitter release at the squid giant synapse. Proc Natl Acad Sci U S A. 1985 May;82(9):3035–3039. doi: 10.1073/pnas.82.9.3035. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Magleby K. L. Facilitation, augmentation, and potentiation of transmitter release. Prog Brain Res. 1979;49:175–182. doi: 10.1016/S0079-6123(08)64631-2. [DOI] [PubMed] [Google Scholar]
- Nestler E. J., Greengard P. Distribution of protein I and regulation of its state of phosphorylation in the rabbit superior cervical ganglion. J Neurosci. 1982 Aug;2(8):1011–1023. doi: 10.1523/JNEUROSCI.02-08-01011.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nestler E. J., Greengard P. Nerve impulses increase the phosphorylation state of protein I in rabbit superior cervical ganglion. Nature. 1982 Apr 1;296(5856):452–454. doi: 10.1038/296452a0. [DOI] [PubMed] [Google Scholar]
- Schiebler W., Jahn R., Doucet J. P., Rothlein J., Greengard P. Characterization of synapsin I binding to small synaptic vesicles. J Biol Chem. 1986 Jun 25;261(18):8383–8390. [PubMed] [Google Scholar]
- Sihra T. S., Wang J. K., Gorelick F. S., Greengard P. Translocation of synapsin I in response to depolarization of isolated nerve terminals. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8108–8112. doi: 10.1073/pnas.86.20.8108. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang J. K., Walaas S. I., Greengard P. Protein phosphorylation in nerve terminals: comparison of calcium/calmodulin-dependent and calcium/diacylglycerol-dependent systems. J Neurosci. 1988 Jan;8(1):281–288. doi: 10.1523/JNEUROSCI.08-01-00281.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]