title: Dynamic Ca2+-dependent stimulation of vesicle fusion by membrane-anchored synaptotagmin 1.
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.
authors.affiliation: Department of Physics, KAIST, Daejeon 305-701, South Korea.
authors.forename: Han-Ki
authors.initials: HK
authors.lastname: Lee
authors.forename: Yoosoo
authors.initials: Y
authors.lastname: Yang
authors.forename: Zengliu
authors.initials: Z
authors.lastname: Su
authors.forename: Changbong
authors.initials: C
authors.lastname: Hyeon
authors.forename: Tae-Sun
authors.initials: TS
authors.lastname: Lee
authors.forename: Hong-Won
authors.initials: HW
authors.lastname: Lee
authors.forename: Dae-Hyuk
authors.initials: DH
authors.lastname: Kweon
authors.forename: Yeon-Kyun
authors.initials: YK
authors.lastname: Shin
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Yoon
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D008561:Membrane Fusion; D008563:Membrane Lipids / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D051381:Rats; D050600:SNARE Proteins / Q000378:metabolism; D013572:Synaptic Vesicles / Q000502:physiology*; D050863:Synaptotagmin I / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008563:Membrane Lipids; D018377:Neurotransmitter Agents; D019269:Phosphatidylinositol 4,5-Diphosphate; D050600:SNARE Proteins; D050863:Synaptotagmin I; D008274:Magnesium; D002118:Calcium
references.citation: Curr Biol. 2008 May 20;18(10):715-722
references.pmid: 18485705
references.citation: Nature. 2007 Nov 29;450(7170):676-82
references.pmid: 18046404
references.citation: BMC Genomics. 2007 Jul 31;8:259
references.pmid: 17672888
references.citation: Nat Struct Mol Biol. 2008 Jul;15(7):707-13
references.pmid: 18552825
references.citation: Nat Struct Mol Biol. 2007 Oct;14(10):904-11
references.pmid: 17891149
references.citation: Annu Rev Biochem. 2008;77:615-41
references.pmid: 18275379
references.citation: Curr Opin Neurobiol. 2005 Jun;15(3):266-74
references.pmid: 15919191
references.citation: Cell. 2004 Jan 23;116(2):153-66
references.pmid: 14744428
references.citation: Annu Rev Neurosci. 2004;27:509-47
references.pmid: 15217342
references.citation: Cell. 1998 Mar 20;92(6):759-72
references.pmid: 9529252
references.citation: Nat Struct Mol Biol. 2004 Jan;11(1):36-44
references.pmid: 14718921
references.citation: Science. 2007 May 25;316(5828):1205-8
references.pmid: 17478680
references.citation: Nat Struct Mol Biol. 2006 Apr;13(4):323-30
references.pmid: 16565726
references.citation: Cell. 2009 Sep 4;138(5):935-46
references.pmid: 19716167
references.citation: Nat Rev Mol Cell Biol. 2006 Sep;7(9):631-43
references.pmid: 16912714
references.citation: Nat Struct Mol Biol. 2008 Jul;15(7):665-74
references.pmid: 18618940
references.citation: Annu Rev Biochem. 2009;78:903-28
references.pmid: 19489736
references.citation: Nat Struct Mol Biol. 2008 Nov;15(11):1160-8
references.pmid: 18953334
references.citation: Biophys J. 2006 Sep 1;91(5):1767-77
references.pmid: 16782782
references.citation: J Cell Biol. 2008 Jul 28;182(2):355-66
references.pmid: 18644890
references.citation: Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19731-6
references.pmid: 17167056
references.citation: Nat Struct Mol Biol. 2006 Mar;13(3):209-17
references.pmid: 16491093
references.citation: J Cell Biol. 2002 Jul 22;158(2):273-82
references.pmid: 12119360
references.citation: Cell. 2009 Aug 21;138(4):709-21
references.pmid: 19703397
references.citation: Neuron. 2002 May 16;34(4):599-611
references.pmid: 12062043
references.citation: Proc Natl Acad Sci U S A. 2009 Jan 27;106(4):979-84
references.pmid: 19164559
references.citation: Nature. 1994 Nov 3;372(6501):55-63
references.pmid: 7969419
references.citation: Cell. 2006 Nov 17;127(4):831-46
references.pmid: 17110340
references.citation: Science. 2004 Apr 16;304(5669):435-8
references.pmid: 15044754