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Journal Article

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

MPS-Authors
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Jahn,  R.
Department of Neurobiology, MPI for biophysical chemistry, Max Planck Society;

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van den Bogaart,  G.
Department of Neurobiology, MPI for biophysical chemistry, Max Planck Society;

Fulltext (public)

1739201.pdf
(Publisher version), 2MB

Supplementary Material (public)

1739201_Suppl_1.pdf
(Supplementary material), 807KB

Citation

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.


Cite as: http://hdl.handle.net/11858/00-001M-0000-000E-F73B-6
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.