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