Home > Research > Publications & Outputs > The C2B Ca2+-binding motif of synaptotagmin is ...

Research

Links

Text available via DOI:

View graph of relations

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

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Published

Standard

The C2B Ca2+-binding motif of synaptotagmin is required for synaptic transmission in vivo. / Mackler, J. M.; Drummond, J. A.; Loewen, C. A. et al.
In: Nature, Vol. 418, No. 6895, 18.07.2002, p. 340-344.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Mackler, JM, Drummond, JA, Loewen, CA, Robinson, IM & Reist, NE 2002, 'The C2B Ca2+-binding motif of synaptotagmin is required for synaptic transmission in vivo', Nature, vol. 418, no. 6895, pp. 340-344. https://doi.org/10.1038/nature00846

APA

Mackler, J. M., Drummond, J. A., Loewen, C. A., Robinson, I. M., & Reist, N. E. (2002). The C2B Ca2+-binding motif of synaptotagmin is required for synaptic transmission in vivo. Nature, 418(6895), 340-344. https://doi.org/10.1038/nature00846

Vancouver

Mackler JM, Drummond JA, Loewen CA, Robinson IM, Reist NE. The C2B Ca2+-binding motif of synaptotagmin is required for synaptic transmission in vivo. Nature. 2002 Jul 18;418(6895):340-344. doi: 10.1038/nature00846

Author

Mackler, J. M. ; Drummond, J. A. ; Loewen, C. A. et al. / The C2B Ca2+-binding motif of synaptotagmin is required for synaptic transmission in vivo. In: Nature. 2002 ; Vol. 418, No. 6895. pp. 340-344.

Bibtex

@article{fd118b9642a941e1b63448997c6e94e0,
title = "The C2B Ca2+-binding motif of synaptotagmin is required for synaptic transmission in vivo",
abstract = "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.",
author = "Mackler, {J. M.} and Drummond, {J. A.} and Loewen, {C. A.} and Robinson, {I. M.} and Reist, {N. E.}",
note = "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-",
year = "2002",
month = jul,
day = "18",
doi = "10.1038/nature00846",
language = "English",
volume = "418",
pages = "340--344",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "6895",

}

RIS

TY - JOUR

T1 - The C2B Ca2+-binding motif of synaptotagmin is required for synaptic transmission in vivo

AU - Mackler, J. M.

AU - Drummond, J. A.

AU - Loewen, C. A.

AU - Robinson, I. M.

AU - Reist, N. E.

N1 - 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-

PY - 2002/7/18

Y1 - 2002/7/18

N2 - 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.

AB - 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.

U2 - 10.1038/nature00846

DO - 10.1038/nature00846

M3 - Journal article

C2 - 12110842

AN - SCOPUS:0037130255

VL - 418

SP - 340

EP - 344

JO - Nature

JF - Nature

SN - 0028-0836

IS - 6895

ER -