Abstract
Synaptotagmin-1 (syt), the putative Ca2+ sensor for exocytosis, is anchored to the membrane of secretory organelles. Its cytoplasmic domain is composed of two Ca2+-sensing modules, C2A and C2B. Syt binds phosphatidylinositol 4,5-bisphosphate (PIP2), a plasma membrane lipid with an essential role in exocytosis and endocytosis. We resolved two modes of PIP2 binding that are mediated by distinct surfaces on the C2B domain of syt. A novel Ca2+-independent mode of binding predisposes syt to penetrate PIP2-harboring target membranes in response to Ca2+ with submillisecond kinetics. Thus, PIP2 increases the speed of response of syt and steers its membrane-penetration activity toward the plasma membrane. We propose that syt-PIP2 interactions are involved in exocytosis by facilitating the close apposition of the vesicle and target membrane on rapid time scales in response to Ca2+.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Calcium Signaling
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Calcium-Binding Proteins*
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Exocytosis
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In Vitro Techniques
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Kinetics
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / metabolism*
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Membrane Lipids / metabolism
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Membrane Proteins / metabolism
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / metabolism*
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Phosphatidylinositol 4,5-Diphosphate / metabolism*
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Protein Binding
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Protein Structure, Tertiary
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Proteolipids / metabolism
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R-SNARE Proteins
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Rats
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Synaptotagmin I
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Synaptotagmins
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Thermodynamics
Substances
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Calcium-Binding Proteins
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Membrane Glycoproteins
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Membrane Lipids
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Membrane Proteins
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Nerve Tissue Proteins
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Phosphatidylinositol 4,5-Diphosphate
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Proteolipids
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R-SNARE Proteins
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Recombinant Proteins
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Synaptotagmin I
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Syt1 protein, rat
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proteoliposomes
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Synaptotagmins