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PMID: 20448186 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Dynamic Ca2+-dependent stimulation of vesicle fusion by membrane-anchored synaptotagmin 1.

Science (New York, N.Y.) ·Vol. 328 ·No. 5979 ·2010-05-07 ·Pages 760-3

Lee HK, Yang Y, Su Z, Hyeon C, Lee TS, Lee HW, Kweon DH, Shin YK, Yoon TY

Abstract

In neurons, synaptotagmin 1 (Syt1) is thought to mediate the fusion of synaptic vesicles with the plasma membrane when presynaptic Ca2+ levels rise. However, in vitro reconstitution experiments have failed to recapitulate key characteristics of Ca2+-triggered membrane fusion. Using an in vitro single-vesicle fusion assay, we found that membrane-anchored Syt1 enhanced Ca2+ sensitivity and fusion speed. This stimulatory activity of membrane-anchored Syt1 dropped as the Ca2+ level rose beyond physiological levels. Thus, Syt1 requires the membrane anchor to stimulate vesicle fusion at physiological Ca2+ levels and may function as a dynamic presynaptic Ca2+ sensor to control the probability of neurotransmitter release.

MeSH Terms
Animals Calcium/metabolism Magnesium/metabolism Membrane Fusion Membrane Lipids/metabolism Neurotransmitter Agents/metabolism Phosphatidylinositol 4,5-Diphosphate/metabolism Rats SNARE Proteins/metabolism Synaptic Vesicles/physiology Synaptotagmin I/chemistry,metabolism
Chemicals
Membrane Lipids Neurotransmitter Agents Phosphatidylinositol 4,5-Diphosphate SNARE Proteins Synaptotagmin I Magnesium Calcium
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Lee Han-Ki
Department of Physics, KAIST, Daejeon 305-701, South Korea.
Yang Yoosoo
Su Zengliu
Hyeon Changbong
Lee Tae-Sun
Lee Hong-Won
Kweon Dae-Hyuk
Shin Yeon-Kyun
Yoon Tae-Young
References (29)
29 references, click to expand
  1. Synaptic vesicles are constitutively active fusion machines that function independently of Ca2+.
    Curr Biol. 2008 May 20;18(10):715-722 PMID: 18485705
  2. A dual-Ca2+-sensor model for neurotransmitter release in a central synapse.
    Nature. 2007 Nov 29;450(7170):676-82 PMID: 18046404
  3. Evolutionary genomics of plant genes encoding N-terminal-TM-C2 domain proteins and the similar FAM62 genes and synaptotagmin genes of metazoans.
    BMC Genomics. 2007 Jul 31;8:259 PMID: 17672888
  4. Complexin and Ca2+ stimulate SNARE-mediated membrane fusion.
    Nat Struct Mol Biol. 2008 Jul;15(7):707-13 PMID: 18552825
  5. Synaptotagmin activates membrane fusion through a Ca2+-dependent trans interaction with phospholipids.
    Nat Struct Mol Biol. 2007 Oct;14(10):904-11 PMID: 17891149
  6. How does synaptotagmin trigger neurotransmitter release?
    Annu Rev Biochem. 2008;77:615-41 PMID: 18275379
  7. Presynaptic calcium and control of vesicle fusion.
    Curr Opin Neurobiol. 2005 Jun;15(3):266-74 PMID: 15919191
  8. The mechanisms of vesicle budding and fusion.
    Cell. 2004 Jan 23;116(2):153-66 PMID: 14744428
  9. The synaptic vesicle cycle.
    Annu Rev Neurosci. 2004;27:509-47 PMID: 15217342
  10. SNAREpins: minimal machinery for membrane fusion.
    Cell. 1998 Mar 20;92(6):759-72 PMID: 9529252
  11. PIP2 increases the speed of response of synaptotagmin and steers its membrane-penetration activity toward the plasma membrane.
    Nat Struct Mol Biol. 2004 Jan;11(1):36-44 PMID: 14718921
  12. How synaptotagmin promotes membrane fusion.
    Science. 2007 May 25;316(5828):1205-8 PMID: 17478680
  13. Ca(2+)-synaptotagmin directly regulates t-SNARE function during reconstituted membrane fusion.
    Nat Struct Mol Biol. 2006 Apr;13(4):323-30 PMID: 16565726
  14. Synaptotagmin-1 docks secretory vesicles to syntaxin-1/SNAP-25 acceptor complexes.
    Cell. 2009 Sep 4;138(5):935-46 PMID: 19716167
  15. SNAREs--engines for membrane fusion.
    Nat Rev Mol Cell Biol. 2006 Sep;7(9):631-43 PMID: 16912714
  16. Synaptic vesicle fusion.
    Nat Struct Mol Biol. 2008 Jul;15(7):665-74 PMID: 18618940
  17. Single-molecule studies of the neuronal SNARE fusion machinery.
    Annu Rev Biochem. 2009;78:903-28 PMID: 19489736
  18. The Janus-faced nature of the C(2)B domain is fundamental for synaptotagmin-1 function.
    Nat Struct Mol Biol. 2008 Nov;15(11):1160-8 PMID: 18953334
  19. Ca2+-triggered simultaneous membrane penetration of the tandem C2-domains of synaptotagmin I.
    Biophys J. 2006 Sep 1;91(5):1767-77 PMID: 16782782
  20. Phosphatidylinositol 4,5-bisphosphate regulates SNARE-dependent membrane fusion.
    J Cell Biol. 2008 Jul 28;182(2):355-66 PMID: 18644890
  21. Multiple intermediates in SNARE-induced membrane fusion.
    Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19731-6 PMID: 17167056
  22. Close membrane-membrane proximity induced by Ca(2+)-dependent multivalent binding of synaptotagmin-1 to phospholipids.
    Nat Struct Mol Biol. 2006 Mar;13(3):209-17 PMID: 16491093
  23. Calcium-independent stimulation of membrane fusion and SNAREpin formation by synaptotagmin I.
    J Cell Biol. 2002 Jul 22;158(2):273-82 PMID: 12119360
  24. Synaptotagmin-mediated bending of the target membrane is a critical step in Ca(2+)-regulated fusion.
    Cell. 2009 Aug 21;138(4):709-21 PMID: 19703397
  25. Ca2+-dependent synaptotagmin binding to SNAP-25 is essential for Ca2+-triggered exocytosis.
    Neuron. 2002 May 16;34(4):599-611 PMID: 12062043
  26. Effects of linker sequences on vesicle fusion mediated by lipid-anchored DNA oligonucleotides.
    Proc Natl Acad Sci U S A. 2009 Jan 27;106(4):979-84 PMID: 19164559
  27. Mechanisms of intracellular protein transport.
    Nature. 1994 Nov 3;372(6501):55-63 PMID: 7969419
  28. Molecular anatomy of a trafficking organelle.
    Cell. 2006 Nov 17;127(4):831-46 PMID: 17110340
  29. Reconstitution of Ca2+-regulated membrane fusion by synaptotagmin and SNAREs.
    Science. 2004 Apr 16;304(5669):435-8 PMID: 15044754
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
Published
2010-05-07
Pages
760-3
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC2994549
Subset
IM
Grants
NIGMS NIH HHS · R01 GM051290 · United States
NIGMS NIH HHS · R01 GM051290-16 · United States
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