Dynamic Ca²⁺-Dependent Stimulation of Vesicle Fusion by Membrane-Anchored Synaptotagmin 1

• Published in: Science (American Association for the Advancement of Science) Vol. 328; no. 5979; pp. 760 - 763
• Main Authors: Lee, Han-Ki, Yang, Yoosoo, Su, Zengliu, Hyeon, Changbong, Lee, Tae-Sun, Lee, Hong-Won, Kweon, Dae-Hyuk, Shin, Yeon-Kyun, Yoon, Tae-Young
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 07.05.2010; The American Association for the Advancement of Science
• Subjects: Animals; Biochemistry; Biological and medical sciences; Calcium - metabolism; Cell membranes; Cellular biology; Fluorescence; Fundamental and applied biological sciences. Psychology; Imaging; Kinetics; Lipids; Magnesium - metabolism; Membrane Fusion; Membrane Lipids - metabolism; Membranes; Neurons; Neurotransmitter Agents - metabolism; Neurotransmitters; Phosphatidylinositol 4,5-Diphosphate - metabolism; Physiological stimulation; Proteins; Rats; rev genes; SNARE Proteins - metabolism; Synaptic Vesicles - physiology; Synaptotagmin I - chemistry; Synaptotagmin I - metabolism; Synaptotagmins; Vertebrates: nervous system and sense organs; Sensitivity; Neuron; Calcium; Synaptic membrane; Plasma membrane; Synaptic vesicle; Stimulation; Synaptotagmin; Experimental study; In vitro; Thought; Presynaptic
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1187722

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.