Linked Life Data

18650324

Source:http://linkedlifedata.com/resource/pubmed/id/18650324

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
30
pubmed:dateCreated
2008-7-24
pubmed:abstractText
Synaptotagmin I is the Ca(2+) sensor for fast, synchronous release of neurotransmitter; however, the molecular interactions that couple Ca(2+) binding to membrane fusion remain unclear. The structure of synaptotagmin is dominated by two C(2) domains that interact with negatively charged membranes after binding Ca(2+). In vitro work has implicated a conserved basic residue at the tip of loop 3 of the Ca(2+)-binding pocket in both C(2) domains in coordinating this electrostatic interaction with anionic membranes. Although results from cultured cells suggest that the basic residue of the C(2)A domain is functionally significant, such studies provide contradictory results regarding the importance of the C(2)B basic residue during vesicle fusion. To directly test the functional significance of each of these residues at an intact synapse in vivo, we neutralized either the C(2)A or the C(2)B basic residue and assessed synaptic transmission at the Drosophila neuromuscular junction. The conserved basic residues at the tip of the Ca(2+)-binding pocket of both the C(2)A and C(2)B domains mediate Ca(2+)-dependent interactions with anionic membranes and are required for efficient evoked transmitter release. Our results directly support the hypothesis that the interactions between synaptotagmin and the presynaptic membrane, which are mediated by the basic residues at the tip of both the C(2)A and C(2)B Ca(2+)-binding pockets, are critical for coupling Ca(2+) influx with vesicle fusion during synaptic transmission in vivo. Our model for synaptotagmin's direct role in coupling Ca(2+) binding to vesicle fusion incorporates this finding with results from multiple in vitro and in vivo studies.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
23
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7458-66
pubmed:dateRevised
2010-12-3
pubmed:meshHeading
pubmed-meshheading:18650324-Acyltransferases, pubmed-meshheading:18650324-Analysis of Variance, pubmed-meshheading:18650324-Animals, pubmed-meshheading:18650324-Animals, Genetically Modified, pubmed-meshheading:18650324-Arginine, pubmed-meshheading:18650324-Calcium, pubmed-meshheading:18650324-Calcium-Binding Proteins, pubmed-meshheading:18650324-Drosophila, pubmed-meshheading:18650324-Drosophila Proteins, pubmed-meshheading:18650324-Electric Stimulation, pubmed-meshheading:18650324-Electrophysiology, pubmed-meshheading:18650324-Embryo, Nonmammalian, pubmed-meshheading:18650324-Excitatory Postsynaptic Potentials, pubmed-meshheading:18650324-Mutagenesis, Site-Directed, pubmed-meshheading:18650324-Neuromuscular Junction, pubmed-meshheading:18650324-Protein Binding, pubmed-meshheading:18650324-Protein Structure, Tertiary, pubmed-meshheading:18650324-Synaptotagmin I
pubmed:year
2008
pubmed:articleTitle
Ca2+-dependent, phospholipid-binding residues of synaptotagmin are critical for excitation-secretion coupling in vivo.
pubmed:affiliation
Department of Biomedical Sciences, Molecular, Cellular, and Integrative Neuroscience Program, Colorado State University, Fort Collins, Colorado 80523-1617, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural