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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 593-605 |
| Number of pages | 13 |
| Journal | Neuron |
| Volume | 23 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jul 1999 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Syntaxin 1A interacts with multiple exocytic proteins to regulate neurotransmitter release in vivo. / Wu, Mark; Fergestad, Tim; Lloyd, Thomas; He, Yuchun; Broadie, Kendal; Bellen, Hugo J.
In: Neuron, Vol. 23, No. 3, 07.1999, p. 593-605.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Syntaxin 1A interacts with multiple exocytic proteins to regulate neurotransmitter release in vivo
AU - Wu, Mark
AU - Fergestad, Tim
AU - Lloyd, Thomas
AU - He, Yuchun
AU - Broadie, Kendal
AU - Bellen, Hugo J.
PY - 1999/7
Y1 - 1999/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0000040564&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0000040564&partnerID=8YFLogxK
U2 - 10.1016/S0896-6273(00)80811-9
DO - 10.1016/S0896-6273(00)80811-9
M3 - Article
C2 - 10433270
AN - SCOPUS:0000040564
VL - 23
SP - 593
EP - 605
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 3
ER -