PIP2 increases the speed of response of synaptotagmin and steers its membrane-penetration activity toward the plasma membrane.
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+.
Bai
Jihong
J
Department of Physiology, University of Wisconsin, Madison, Wisconsin 53706, USA.
Tucker
Ward C
WC
Chapman
Edwin R
ER
D000818:Animals; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins; D005089:Exocytosis; D066298:In Vitro Techniques; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011510:Proteolipids / Q000378:metabolism; D050683:R-SNARE Proteins; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D050863:Synaptotagmin I; D050857:Synaptotagmins; D013816:Thermodynamics
D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D008563:Membrane Lipids; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D011510:Proteolipids; D050683:R-SNARE Proteins; D011994:Recombinant Proteins; D050863:Synaptotagmin I; C494312:Syt1 protein, rat; C020485:proteoliposomes; D050857:Synaptotagmins