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  Synaptic PI(3,4,5)P-3 is required for Syntaxin1A clustering and neurotransmitter release.

Khuong, T. M., Habets, R. L. P., Kuenen, S., Witkowska, A., Kasprowicz, J., Swerts, J., et al. (2013). Synaptic PI(3,4,5)P-3 is required for Syntaxin1A clustering and neurotransmitter release. Neuron, 77(6), 1097-1108. doi:10.1016/j.neuron.2013.01.025.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-F73B-6 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-1F72-6
Genre: Journal Article

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 Creators:
Khuong, T. M., Author
Habets, R. L. P., Author
Kuenen, S., Author
Witkowska, A., Author
Kasprowicz, J., Author
Swerts, J., Author
Jahn, R.1, Author              
van den Bogaart, G.1, Author              
Verstreken, P., Author
Affiliations:
1Department of Neurobiology, MPI for biophysical chemistry, Max Planck Society, ou_578595              

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 Abstract: PI(3,4,5)P-3 is a low-abundance lipid thought to play a role in the regulation of synaptic activity; however, the mechanism remains obscure. We have constructed novel split Venus-based probes and used superresolution imaging to localize PI(3,4,5)P-3 at Drosophila larval neuromuscular synapses. We find the lipid in membrane domains at neurotransmitter release sites, where it concentrates with Syntaxin1A, a protein essential for vesicle fusion. Reducing PI(3,4,5)P-3 availability disperses Syntaxin1A clusters and increasing PI(3,4,5)P-3 levels rescues this defect. In artificial giant unilamellar vesicles, PI(3,4,5)P-3 also induces Syntaxin1A domain formation and this clustering, in vitro and in vivo, is dependent on positively charged residues in the Syntaxin1A-juxtannembrane domain. Functionally, reduced PI(3,4,5)P-3 causes temperature-sensitive paralysis and reduced neurotransmitter release, a phenotype also seen in animals expressing a Syntaxin1A with a mutated juxtamembrane domain. Thus, our data indicate that PI(3,4,5)P-3, based on electrostatic interactions, clusters Syntaxin1A at release sites to regulate neurotransmitter release.

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Language(s): eng - English
 Dates: 2013-03-20
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.neuron.2013.01.025
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Title: Neuron
Source Genre: Journal
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Pages: - Volume / Issue: 77 (6) Sequence Number: - Start / End Page: 1097 - 1108 Identifier: -