Different domains of synaptotagmin control the choice between kiss-and-run and full fusion

Exocytosis-the release of the contents of a vesicle-proceeds by two mechanisms. Full fusion occurs when the vesicle and plasma membranes merge. Alternatively, in what is termed kiss-and-run, vesicles can release transmitter during transient contacts with the plasma membrane. Little is known at the m...

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Bibliographic Details
Published in:Nature 2003-08, Vol.424 (6951), p.943-947
Main Authors: Jackson, Meyer B, Wang, Chih-Tien, Lu, Juu-Chin, Bai, Jihong, Chang, Payne Y, Martin, Thomas F. J, Chapman, Edwin R
Format: Article
Language:English
Subjects:
Animals
Binding Sites
Biological and medical sciences
Calcium - metabolism
Calcium-Binding Proteins
Cell Membrane - metabolism
Cell Membrane Permeability
Cell physiology
Colforsin - pharmacology
Exocytosis
Fundamental and applied biological sciences. Psychology
Fusion
Ligands
Membrane Fusion
Membrane Glycoproteins - chemistry
Membrane Glycoproteins - genetics
Membrane Glycoproteins - metabolism
Membranes
Molecular and cellular biology
Mutation
Mutation - genetics
Nerve Tissue Proteins - chemistry
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
PC12 Cells
Plasma
Protein Binding
Protein Structure, Tertiary
Rats
Secretion. Exocytosis
Synaptotagmins
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Summary:Exocytosis-the release of the contents of a vesicle-proceeds by two mechanisms. Full fusion occurs when the vesicle and plasma membranes merge. Alternatively, in what is termed kiss-and-run, vesicles can release transmitter during transient contacts with the plasma membrane. Little is known at the molecular level about how the choice between these two pathways is regulated. Here we report amperometric recordings of catecholamine efflux through individual fusion pores. Transfection with synaptotagmin (Syt) IV increased the frequency and duration of kiss-and-run events, but left their amplitude unchanged. Endogenous Syt IV, induced by forskolin treatment, had a similar effect. Full fusion was inhibited by mutation of a Ca2+ ligand in the C2A domain of Syt I; kiss-and-run was inhibited by mutation of a homologous Ca2+ ligand in the C2B domain of Syt IV. The Ca2+ sensitivity for full fusion was 5-fold higher with Syt I than Syt IV, but for kiss-and-run the Ca2+ sensitivities differed by a factor of only two. Syt thus regulates the choice between full fusion and kiss-and-run, with Ca2+ binding to the C2A and C2B domains playing an important role in this choice.
ISSN:0028-0836
1476-4687
DOI:10.1038/nature01857