@article{90670d87ea584950ba44ad805e68d356,
title = "Syntaxin 1A interacts with multiple exocytic proteins to regulate neurotransmitter release in vivo",
abstract = "Biochemical studies suggest that syntaxin 1A participates in multiple protein-protein interactions in the synaptic terminal, but the in vivo significance of these interactions is poorly understood. We used a targeted mutagenesis approach to eliminate specific syntaxin binding interactions and demonstrate that Drosophila syntaxin 1A plays multiple regulatory roles in neurotransmission in vivo. Syntaxin mutations that eliminate ROP/Munc-18 binding display increased neurotransmitter release, suggesting that ROP inhibits neurosecretion through its interaction with syntaxin. Syntaxin mutations that block Ca2+ channel binding also cause an increase in neurotransmitter release, suggesting that syntaxin normally functions in inhibiting Ca2+ channel opening. Additionally, we identify and characterize a syntaxin Ca2+ effector domain, which may spatially organize the Ca2+ channel, cysteine string protein, and synaptotagmin for effective excitation- secretion coupling in the presynaptic terminal.",
author = "Wu, {Mark N.} and Tim Fergestad and Lloyd, {Thomas E.} and Yuchun He and Kendal Broadie and Bellen, {Hugo J.}",
note = "Funding Information: We thank G. Bhave and K. Schulze for help with binding assays. We are grateful to D. Casso and T. Kornberg for sharing their Kr GFP balancer flies with us prior to publication. We thank J. Roos, R. Kelly, T. S{\"u}dhof, R. Jahn, and K. Zinsmaier for providing antibodies. We also thank T. Schwarz, B. McCabe, C. O'Kane, J. T. Littleton, W. Caterall, and K. Zinsmaier for providing DNA constructs. For the protocol for coimmunoprecipitation of CSP and Syx, we thank J. Wenniger and K. Zinsmaier. We thank M. L. Zhao for help with calcium-free recordings. We thank A. Bean, E. Chapman, and B. Dickey for helpful comments and advice on this manuscript. We also acknowledge members of the Bellen and Broadie labs for critically reading this manuscript. M. N. W. and T. E. L. are supported by predoctoral NIMH National Research Service Award training grants. T. F. is supported by an NIH Developmental Biology Training Grant, and K. B. is funded by the NIH (GM54544) and a Searle Scholarship. This work was supported by an NIH grant to H. J. B. and by the Howard Hughes Medical Institute (HHMI). H. J. B. is an associate investigator of the HHMI.",
year = "1999",
month = jul,
doi = "10.1016/S0896-6273(00)80811-9",
language = "English (US)",
volume = "23",
pages = "593--605",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "3",
}