Dynamic Ca 2+ -Dependent Stimulation of Vesicle Fusion by Membrane-Anchored Synaptotagmin 1

• DOI: 10.1126/science.1187722
• Publication Date: 2010-05-06T18:53:23Z
• Authors: Han-Ki Lee; Yoosoo Yang; Zengliu Su; Changbong Hyeon; Tae-Sun Lee; Hong-Won Lee; Dae-Hyuk Kweon; Yeon-Kyun Shin; Tae-Young Yoon
• Keywords: Phosphatidylinositol 4,5-Diphosphate; Neurotransmitter Agents; 0303 health sciences; Membrane Fusion; Rats; Membrane Lipids; 03 medical and health sciences; Synaptotagmin I; Animals; Calcium; Magnesium; Synaptic Vesicles; SNARE Proteins

In neurons, synaptotagmin 1 (Syt1) is thought to mediate the fusion of synaptic vesicles with the plasma membrane when presynaptic Ca2+ levels rise. However, in vitro reconstitution experiments have failed to recapitulate key characteristics of Ca2+-triggered membrane fusion. Using an in vitro single-vesicle fusion assay, we found that membrane-anchored Syt1 enhanced Ca2+ sensitivity and fusion speed. This stimulatory activity of membrane-anchored Syt1 dropped as the Ca2+ level rose beyond physiological levels. Thus, Syt1 requires the membrane anchor to stimulate vesicle fusion at physiological Ca2+ levels and may function as a dynamic presynaptic Ca2+ sensor to control the probability of neurotransmitter release.