Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 2 November 2001:
Vol. 294. no. 5544, pp. 1111 - 1115
DOI: 10.1126/science.1064002
Prev | Table of Contents | Next

Reports

Synaptotagmin Modulation of Fusion Pore Kinetics in Regulated Exocytosis of Dense-Core Vesicles

Chih-Tien Wang,1 Ruslan Grishanin,2 Cynthia A. Earles,1 Payne Y. Chang,1 Thomas F. J. Martin,2 Edwin R. Chapman,1 Meyer B. Jackson1*

In the exocytosis of neurotransmitter, fusion pore opening represents the first instant of fluid contact between the vesicle lumen and extracellular space. The existence of the fusion pore has been established by electrical measurements, but its molecular composition is unknown. The possibility that synaptotagmin regulates fusion pores was investigated with amperometry to monitor exocytosis of single dense-core vesicles. Overexpression of synaptotagmin I prolonged the time from fusion pore opening to dilation, whereas synaptotagmin IV shortened this time. Both synaptotagmin isoforms reduced norepinephrine flux through open fusion pores. Thus, synaptotagmin interacts with fusion pores, possibly by associating with a core complex of membrane proteins and/or lipid.

1 Department of Physiology, University of Wisconsin Medical School,
2 Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA.
*   To whom correspondence should be addressed. E-mail: mjackson{at}physiology.wisc.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Regulation of quantal shape by Rab3A: evidence for a fusion pore-dependent mechanism.
X. Wang, R. Thiagarajan, Q. Wang, T. Tewolde, M. M. Rich, and K. L. Engisch (2008)
J. Physiol. 586, 3949-3962
   Abstract »    Full Text »    PDF »
Analysis of the Synaptotagmin Family during Reconstituted Membrane Fusion: UNCOVERING A CLASS OF INHIBITORY ISOFORMS.
A. Bhalla, M. C. Chicka, and E. R. Chapman (2008)
J. Biol. Chem. 283, 21799-21807
   Abstract »    Full Text »    PDF »
DOC2B Acts as a Calcium Switch and Enhances Vesicle Fusion.
R. Friedrich, A. J. Groffen, E. Connell, J. R. T. van Weering, O. Gutman, Y. I. Henis, B. Davletov, and U. Ashery (2008)
J. Neurosci. 28, 6794-6806
   Abstract »    Full Text »    PDF »
Myosin II Contributes to Fusion Pore Expansion during Exocytosis.
P. Neco, C. Fernandez-Peruchena, S. Navas, L. M. Gutierrez, G. A. de Toledo, and E. Ales (2008)
J. Biol. Chem. 283, 10949-10957
   Abstract »    Full Text »    PDF »
Nonredundant function of secretory carrier membrane protein isoforms in dense core vesicle exocytosis.
H. Liao, J. Zhang, S. Shestopal, G. Szabo, A. Castle, and D. Castle (2008)
Am J Physiol Cell Physiol 294, C797-C809
   Abstract »    Full Text »    PDF »
Munc-18-1 Regulates the Initial Release Rate of Exocytosis.
J. W. Barclay (2008)
Biophys. J. 94, 1084-1093
   Abstract »    Full Text »    PDF »
Temperature Dependence of Fusion Kinetics and Fusion Pores in Ca2+-triggered Exocytosis from PC12 Cells.
Z. Zhang and M. B. Jackson (2008)
J. Gen. Physiol. 131, 117-124
   Abstract »    Full Text »    PDF »
Elementary properties of spontaneous fusion of peptidergic vesicles: fusion pore gating.
N. Vardjan, M. Stenovec, J. Jorgacevski, M. Kreft, and R. Zorec (2007)
J. Physiol. 585, 655-661
   Abstract »    Full Text »    PDF »
Stable RNA interference of synaptotagmin I in PC12 cells results in differential regulation of transmitter release.
W. H. Roden, J. B. Papke, J. M. Moore, A. L. Cahill, H. Macarthur, and A. B. Harkins (2007)
Am J Physiol Cell Physiol 293, C1742-C1752
   Abstract »    Full Text »    PDF »
Gbeta{gamma} Interferes with Ca2+-Dependent Binding of Synaptotagmin to the Soluble N-Ethylmaleimide-Sensitive Factor Attachment Protein Receptor (SNARE) Complex.
E.-J. Yoon, T. Gerachshenko, B. D. Spiegelberg, S. Alford, and H. E. Hamm (2007)
Mol. Pharmacol. 72, 1210-1219
   Abstract »    Full Text »    PDF »
Dynamic Regulation of the Large Exocytotic Fusion Pore in Pancreatic Acinar Cells.
O. Larina, P. Bhat, J. A. Pickett, B. S. Launikonis, A. Shah, W. A. Kruger, J. M. Edwardson, and P. Thorn (2007)
Mol. Biol. Cell 18, 3502-3511
   Abstract »    Full Text »    PDF »
Characterization of the role of the Synaptotagmin family as calcium sensors in facilitation and asynchronous neurotransmitter release.
S. Saraswati, B. Adolfsen, and J. T. Littleton (2007)
PNAS 104, 14122-14127
   Abstract »    Full Text »    PDF »
Influence of Quantal Size and cAMP on the Kinetics of Quantal Catecholamine Release from Rat Chromaffin Cells.
K. S. Tang, N. Wang, A. Tse, and F. W. Tse (2007)
Biophys. J. 92, 2735-2746
   Abstract »    Full Text »    PDF »
Synaptotagmins I and IX function redundantly in regulated exocytosis but not endocytosis in PC12 cells.
K. L. Lynch and T. F. J. Martin (2007)
J. Cell Sci. 120, 617-627
   Abstract »    Full Text »    PDF »
Distinct role of Rab3A and Rab3B in secretory activity of rat melanotrophs.
M. Rupnik, M. Kreft, F. Nothias, S. Grilc, L. K. Bobanovic, L. Johannes, T. Kiauta, P. Vernier, F. Darchen, and R. Zorec (2007)
Am J Physiol Cell Physiol 292, C98-C105
   Abstract »    Full Text »    PDF »
C2B Polylysine Motif of Synaptotagmin Facilitates a Ca2+-independent Stage of Synaptic Vesicle Priming In Vivo.
C. A. Loewen, S.-M. Lee, Y.-K. Shin, and N. E. Reist (2006)
Mol. Biol. Cell 17, 5211-5226
   Abstract »    Full Text »    PDF »
A Gain-of-Function Mutation in Synaptotagmin-1 Reveals a Critical Role of Ca2+-Dependent Soluble N-Ethylmaleimide-Sensitive Factor Attachment Protein Receptor Complex Binding in Synaptic Exocytosis.
Z. P. Pang, O.-H. Shin, A. C. Meyer, C. Rosenmund, and T. C. Sudhof (2006)
J. Neurosci. 26, 12556-12565
   Abstract »    Full Text »    PDF »
Astrocyte control of synaptic transmission and neurovascular coupling..
P. G. Haydon and G. Carmignoto (2006)
Physiol Rev 86, 1009-1031
   Abstract »    Full Text »    PDF »
Synaptotagmin IV is necessary for the maturation of secretory granules in PC12 cells.
M. Ahras, G. P. Otto, and S. A. Tooze (2006)
J. Cell Biol. 173, 241-251
   Abstract »    Full Text »    PDF »
A novel form of immune signaling revealed by transmission of the inflammatory mediator serotonin between dendritic cells and T cells.
P. J. O'Connell, X. Wang, M. Leon-Ponte, C. Griffiths, S. C. Pingle, and G. P. Ahern (2006)
Blood 107, 1010-1017
   Abstract »    Full Text »    PDF »
Structural transitions in the synaptic SNARE complex during Ca2+-triggered exocytosis.
X. Han and M. B. Jackson (2006)
J. Cell Biol. 172, 281-293
   Abstract »    Full Text »    PDF »
Synaptotagmin-Ca2+ triggers two sequential steps in regulated exocytosis in rat PC12 cells: fusion pore opening and fusion pore dilation.
C.-T. Wang, J. Bai, P. Y. Chang, E. R. Chapman, and M. B. Jackson (2006)
J. Physiol. 570, 295-307
   Abstract »    Full Text »    PDF »
Synaptotagmin IV Does Not Alter Excitatory Fast Synaptic Transmission or Fusion Pore Kinetics in Mammalian CNS Neurons.
J. T. Ting, B. G. Kelley, and J. M. Sullivan (2006)
J. Neurosci. 26, 372-380
   Abstract »    Full Text »    PDF »
SCAMP2 Interacts with Arf6 and Phospholipase D1 and Links Their Function to Exocytotic Fusion Pore Formation in PC12 Cells.
L. Liu, H. Liao, A. Castle, J. Zhang, J. Casanova, G. Szabo, and D. Castle (2005)
Mol. Biol. Cell 16, 4463-4472
   Abstract »    Full Text »    PDF »
Selective nucleotide-release from dense-core granules in insulin-secreting cells.
S. Obermuller, A. Lindqvist, J. Karanauskaite, J. Galvanovskis, P. Rorsman, and S. Barg (2005)
J. Cell Sci. 118, 4271-4282
   Abstract »    Full Text »    PDF »
Amisyn Regulates Exocytosis and Fusion Pore Stability by Both Syntaxin-dependent and Syntaxin-independent Mechanisms.
J. R. L. Constable, M. E. Graham, A. Morgan, and R. D. Burgoyne (2005)
J. Biol. Chem. 280, 31615-31623
   Abstract »    Full Text »    PDF »
Correlation between Vesicle Quantal Size and Fusion Pore Release in Chromaffin Cell Exocytosis.
C. Amatore, S. Arbault, I. Bonifas, Y. Bouret, M. Erard, A. G. Ewing, and L. A. Sombers (2005)
Biophys. J. 88, 4411-4420
   Abstract »    Full Text »    PDF »
Phosphatidylinositol phosphate kinase type I{gamma} regulates dynamics of large dense-core vesicle fusion.
L.-W. Gong, G. Di Paolo, E. Diaz, G. Cestra, M.-E. Diaz, M. Lindau, P. De Camilli, and D. Toomre (2005)
PNAS 102, 5204-5209
   Abstract »    Full Text »    PDF »
Electrostatic Interactions between the Syntaxin Membrane Anchor and Neurotransmitter Passing through the Fusion Pore.
X. Han and M. B. Jackson (2005)
Biophys. J. 88, L20-L22
   Abstract »    Full Text »    PDF »
EBAG9 Adds a New Layer of Control on Large Dense-Core Vesicle Exocytosis via Interaction with Snapin.
C. Ruder, T. Reimer, I. Delgado-Martinez, R. Hermosilla, A. Engelsberg, R. Nehring, B. Dorken, and A. Rehm (2005)
Mol. Biol. Cell 16, 1245-1257
   Abstract »    Full Text »    PDF »
Cycling of Synaptic Vesicles: How Far? How Fast!.
T. Galli and V. Haucke (2004)
Sci. STKE 2004, re19
   Abstract »    Full Text »    PDF »
The Synaptotagmins: Calcium Sensors for Vesicular Trafficking.
M. Yoshihara and E. S. Montana (2004)
Neuroscientist 10, 566-574
   Abstract »    PDF »
Crystallographic identification of Ca2+ and Sr2+ coordination sites in synaptotagmin I C2B domain.
Y. Cheng, S. M. Sequeira, L. Malinina, V. Tereshko, T. H. Sollner, and D. J. Patel (2004)
Protein Sci. 13, 2665-2672
   Abstract »    Full Text »    PDF »
Quantal release of ATP from clusters of PC12 cells.
A. Fabbro, A. Skorinkin, M. Grandolfo, A. Nistri, and R. Giniatullin (2004)
J. Physiol. 560, 505-517
   Abstract »    Full Text »    PDF »
Regulation of the Fusion Pore Conductance during Exocytosis by Cyclin-dependent Kinase 5.
J. W. Barclay, M. Aldea, T. J. Craig, A. Morgan, and R. D. Burgoyne (2004)
J. Biol. Chem. 279, 41495-41503
   Abstract »    Full Text »    PDF »
Effect of Forskolin on Synaptotagmin IV Protein Trafficking in PC12 Cells.
M. Fukuda and A. Yamamoto (2004)
J. Biochem. 136, 245-253
   Abstract »    Full Text »    PDF »
Synaptotagmins are trafficked to distinct subcellular domains including the postsynaptic compartment.
B. Adolfsen, S. Saraswati, M. Yoshihara, and J. T. Littleton (2004)
J. Cell Biol. 166, 249-260
   Abstract »    Full Text »    PDF »
Transmembrane Segments of Syntaxin Line the Fusion Pore of Ca2+-Triggered Exocytosis.
X. Han, C.-T. Wang, J. Bai, E. R. Chapman, and M. B. Jackson (2004)
Science 304, 289-292
   Abstract »    Full Text »    PDF »
SNAP-23 Functions in Docking/Fusion of Granules at Low Ca2+.
E. Chieregatti, M. C. Chicka, E. R. Chapman, and G. Baldini (2004)
Mol. Biol. Cell 15, 1918-1930
   Abstract »    Full Text »    PDF »
Mutations in the Effector Binding Loops in the C2A and C2B Domains of Synaptotagmin I Disrupt Exocytosis in a Nonadditive Manner.
P. Wang, C.-T. Wang, J. Bai, M. B. Jackson, and E. R. Chapman (2003)
J. Biol. Chem. 278, 47030-47037
   Abstract »    Full Text »    PDF »
The autosomal recessive juvenile Parkinson disease gene product, parkin, interacts with and ubiquitinates synaptotagmin XI.
D. P. Huynh, D. R. Scoles, D. Nguyen, and S. M. Pulst (2003)
Hum. Mol. Genet. 12, 2587-2597
   Abstract »    Full Text »    PDF »
Synaptotagmin Function Illuminated.
M. Lindau (2003)
J. Gen. Physiol. 122, 251-254
   Full Text »    PDF »
Examining Synaptotagmin 1 Function in Dense Core Vesicle Exocytosis under Direct Control of Ca2+.
J. B. Sorensen, R. Fernandez-Chacon, T. C. Sudhof, and E. Neher (2003)
J. Gen. Physiol. 122, 265-276
   Abstract »    Full Text »    PDF »
Expression of Mutant Huntingtin Blocks Exocytosis in PC12 Cells by Depletion of Complexin II.
J. M. Edwardson, C.-T. Wang, B. Gong, A. Wyttenbach, J. Bai, M. B. Jackson, E. R. Chapman, and A. J. Morton (2003)
J. Biol. Chem. 278, 30849-30853
   Abstract »    Full Text »    PDF »
Identification of synaptotagmin effectors via acute inhibition of secretion from cracked PC12 cells.
W. C. Tucker, J. M. Edwardson, J. Bai, H.-J. Kim, T. F.J. Martin, and E. R. Chapman (2003)
J. Cell Biol. 162, 199-209
   Abstract »    Full Text »    PDF »
Secretory Granule Exocytosis.
R. D. Burgoyne and A. Morgan (2003)
Physiol Rev 83, 581-632
   Abstract »    Full Text »    PDF »
Visualization of synaptotagmin I oligomers assembled onto lipid monolayers.
Y. Wu, Y. He, J. Bai, S.-R. Ji, W. C. Tucker, E. R. Chapman, and S.-F. Sui (2003)
PNAS 100, 2082-2087
   Abstract »    Full Text »    PDF »
Synaptotagmin I increases the probability of vesicle fusion at low [Ca2+] in pituitary cells.
M. Kreft, V. Kuster, S. Grilc, M. Rupnik, I. Milisav, and R. Zorec (2003)
Am J Physiol Cell Physiol 284, C547-C554
   Abstract »    Full Text »    PDF »
Nerve Growth Factor-dependent Sorting of Synaptotagmin IV Protein to Mature Dense-core Vesicles That Undergo Calcium-dependent Exocytosis in PC12 Cells.
M. Fukuda, E. Kanno, Y. Ogata, C. Saegusa, T. Kim, Y. P. Loh, and A. Yamamoto (2003)
J. Biol. Chem. 278, 3220-3226
   Abstract »    Full Text »    PDF »
Role of Secretory Carrier Membrane Protein SCAMP2 in Granule Exocytosis.
L. Liu, Z. Guo, Q. Tieu, A. Castle, and D. Castle (2002)
Mol. Biol. Cell 13, 4266-4278
   Abstract »    Full Text »    PDF »
Perturbation of a Very Late Step of Regulated Exocytosis by a Secretory Carrier Membrane Protein (SCAMP2)-derived Peptide.
Z. Guo, L. Liu, D. Cafiso, and D. Castle (2002)
J. Biol. Chem. 277, 35357-35363
   Abstract »    Full Text »    PDF »
The Calcium-binding Loops of the Tandem C2 Domains of Synaptotagmin VII Cooperatively Mediate Calcium-dependent Oligomerization.
M. Fukuda, E. Katayama, and K. Mikoshiba (2002)
J. Biol. Chem. 277, 29315-29320
   Abstract »    Full Text »    PDF »
Calcium-independent stimulation of membrane fusion and SNAREpin formation by synaptotagmin I.
L. K. Mahal, S. M. Sequeira, J. M. Gureasko, and T. H. Sollner (2002)
J. Cell Biol. 158, 273-282
   Abstract »    Full Text »    PDF »
Direct, Ca2+-dependent Interaction between Tubulin and Synaptotagmin I. A POSSIBLE MECHANISM FOR ATTACHING SYNAPTIC VESICLES TO MICROTUBULES.
A. Honda, M. Yamada, H. Saisu, H. Takahashi, K. J. Mori, and T. Abe (2002)
J. Biol. Chem. 277, 20234-20242
   Abstract »    Full Text »    PDF »
Complexin Regulates the Closure of the Fusion Pore during Regulated Vesicle Exocytosis.
D. A. Archer, M. E. Graham, and R. D. Burgoyne (2002)
J. Biol. Chem. 277, 18249-18252
   Abstract »    Full Text »    PDF »
C2A activates a cryptic Ca2+-triggered membrane penetration activity within the C2B domain of synaptotagmin I.
J. Bai, P. Wang, and E. R. Chapman (2002)
PNAS
   Abstract »    Full Text »    PDF »
C2A activates a cryptic Ca2+-triggered membrane penetration activity within the C2B domain of synaptotagmin I.
J. Bai, P. Wang, and E. R. Chapman (2002)
PNAS 99, 1665-1670
   Abstract »    Full Text »    PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)