Article

How does synaptotagmin trigger neurotransmitter release?

Howard Hughes Medical Institute and Department of Physiology, University of Wisconsin, Madison, WI 53706, USA.
Annual Review of Biochemistry (Impact Factor: 26.53). 02/2008; 77:615-41. DOI: 10.1146/annurev.biochem.77.062005.101135
Source: PubMed

ABSTRACT Neurotransmitter release at synapses involves a highly specialized form of membrane fusion that is triggered by Ca(2+) ions and is optimized for speed. These observations were established decades ago, but only recently have the molecular mechanisms that underlie this process begun to come into view. Here, we summarize findings obtained from genetically modified neurons and neuroendocrine cells, as well as from reconstituted systems, which are beginning to reveal the molecular mechanism by which Ca(2+)-acting on the synaptic vesicle (SV) protein synaptotagmin I (syt)-triggers rapid exocytosis. This work sheds light not only on presynaptic aspects of synaptic transmission, but also on the fundamental problem of membrane fusion, which has remained a puzzle that has yet to be solved in any biological system.

2 Bookmarks
 · 
153 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The halotolerant green algae Dunaliella bardawil is unique in that it accumulates under stress two types of lipid droplets: cytoplasmatic lipid droplets (CLD) and β-carotene-rich plastoglobuli (βC-plastoglobuli). Recently we isolated and analyzed the lipid and pigment compositions of these lipid droplets. Here we describe their proteome analysis. A contamination filter and an enrichment filter were utilized to define core proteins. A proteome database of D. salina/D. bardawil was constructed to aid identification of lipid droplets proteins. A total of 124 and 42 core proteins were identified in βC-plastoglobuli and in CLD, respectively, with only 8 common proteins. Dunaliella CLD resemble cytoplasmic droplets from C. reinhardtii and contain major lipid droplet associated protein (MLDP) and enzymes involved in lipid and sterol metabolism. βC-plastoglobuli proteome resembles C. reinhardtii eyespot and A. thaliana plastoglobules proteomes and contain carotene-globule-associated protein (CGP), PAP-fibrillins, SOUL heme-binding proteins, phytyl-ester synthases (PES), β-carotene biosynthesis enzymes and proteins involved in membrane remodeling/lipid droplets biogenesis: vesicle-inducing plastid protein 1 (VIPP1), synaptotagmin and the eyespot assembly proteins EYE3 and SOUL3. Based on these and previous results we propose models for biogenesis of βC-plastoglobuli, for biosynthesis of β-carotene within βC-plastoglobuli and hypothesize that βC-plastoglobuli evolved from eyespot lipid droplets. Copyright © 2014, American Society of Plant Biologists.
    Plant physiology 11/2014; · 7.39 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Synaptotagmins are a large gene family in animals that have been extensively characterized due to their role as calcium sensors to regulate synaptic vesicle exocytosis and endocytosis in neurons, and dense core vesicle exocytosis for hormone secretion from neuroendocrine cells. Thought to be exclusive to animals, synaptotagmins have recently been characterized in Arabidopsis thaliana, in which they comprise a five gene family. Using infectivity and leaf-based functional assays, we have shown that Arabidopsis SYTA regulates endocytosis and marks an endosomal vesicle recycling pathway to regulate movement protein-mediated trafficking of the Begomovirus Cabbage leaf curl virus (CaLCuV) and the Tobamovirus Tobacco mosaic virus (TMV) through plasmodesmata (Lewis and Lazarowitz, 2010). To determine whether SYTA has a central role in regulating the cell-to-cell trafficking of a wider range of diverse plant viruses, we extended our studies here to examine the role of SYTA in the cell-to-cell movement of additional plant viruses that employ different modes of movement, namely the Potyvirus Turnip mosaic virus (TuMV), the Caulimovirus Cauliflower mosaic virus (CaMV) and the Tobamovirus Turnip vein clearing virus (TVCV), which in contrast to TMV does efficiently infect Arabidopsis. We found that both TuMV and TVCV systemic infection, and the cell-to-cell trafficking of the their movement proteins, were delayed in the Arabidopsis Col-0 syta-1 knockdown mutant. In contrast, CaMV systemic infection was not inhibited in syta-1. Our studies show that SYTA is a key regulator of plant virus intercellular movement, being necessary for the ability of diverse cell-to-cell movement proteins encoded by Begomoviruses (CaLCuV MP), Tobamoviruses (TVCV and TMV 30K protein) and Potyviruses (TuMV P3N-PIPO) to alter PD and thereby mediate virus cell-to-cell spread.
    Frontiers in Plant Science 11/2014; 5:584. · 3.64 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Fast synchronous neurotransmitter release is triggered by calcium that activates synaptotagmin-1 (syt-1), resulting in fusion of synaptic vesicles with the presynaptic membrane. Syt-1 possesses two Ca(2+)-binding C2 domains that tether membranes via interactions with anionic phospholipids. It is capable of crosslinking membranes and has recently been speculated to trigger fusion by decreasing the gap between them. As quantitative information on membrane gaps is key to understanding general cellular mechanisms, including the role of syt-1, we developed a fluorescence-lifetime based inter-membrane distance ruler using membrane-anchored DNAs of various lengths as calibration standards. Wild-type and mutant data provide evidence that full-length syt-1 indeed regulates membrane gaps: without Ca(2+), syt-1 maintains membranes at distances of ~7-8 nm. Activation with 100 μM Ca(2+) decreases the distance to ~5 nm by binding the C2 domains to opposing membranes, respectively. These values reveal that activated syt-1 adjusts membrane distances to the level that promotes SNARE complex assembly.
    Nature Communications 01/2014; 5:5859. · 10.74 Impact Factor

Preview

Download
5 Downloads
Available from