The C2B Ca2+-binding motif of synaptotagmin is required for synaptic transmission in vivo

Mackler, J. M. and Drummond, J. A. and Loewen, C. A. and Robinson, I. M. and Reist, N. E. (2002) The C2B Ca2+-binding motif of synaptotagmin is required for synaptic transmission in vivo. Nature, 418 (6895). pp. 340-344. ISSN 0028-0836

Full text not available from this repository.


Synaptotagmin is a synaptic vesicle protein that is postulated to be the Ca2+ sensor for fast, evoked neurotransmitter release. Deleting the gene for synaptotagmin (sytnull) strongly suppresses synaptic transmission in every species examined, showing that synaptotagmin is central in the synaptic vesicle cycle. The cytoplasmic region of synaptotagmin contains two C2 domains, C2A and C2B. Five, highly conserved, acidic residues in both the C2A and C2B domains of synaptotagmin coordinate the binding of Ca2+ ions, and biochemical studies have characterized several in vitro Ca2+-dependent interactions between synaptotagmin and other nerve terminal molecules. But there has been no direct evidence that any of the Ca2+-binding sites within synaptotagmin are required in vivo. Here we show that mutating two of the Ca2+-binding aspartate residues in the C2B domain (D416, 418N in Drosophila) decreased evoked transmitter release by >95%, and decreased the apparent Ca2+ affinity of evoked transmitter release. These studies show that the Ca2+-binding motif of the C2B domain of synaptotagmin is essential for synaptic transmission.

Item Type:
Journal Article
Journal or Publication Title:
Additional Information:
Funding Information: We thank I. Inman for technical assistance; N. Reist, J. Li Bryan Stewart and B. Niemeyer for reagents and discussions; and N. Gay and the Department of Biochemistry (Cambridge) for resources. I.M.R. was supported by the American Heart Association, Western Affiliate, and is a Medical Research Council Career Development Award Fellow. The work was supported by the Muscular Dystrophy Association, by a Silvio Conti Center for Neuroscience Award from the National Institute of Mental Health, and by the National Institutes of Health (T.L.S.). Funding Information: The C2B domain of synaptotagmin has been proposed to take part in vesicle recycling17. This hypothesis is supported by ultra-
Uncontrolled Keywords:
ID Code:
Deposited By:
Deposited On:
13 Sep 2023 13:45
Last Modified:
18 Sep 2023 02:17