Functional specificity of liquid-liquid phase separation at the synapse.
| Title: | Functional specificity of liquid-liquid phase separation at the synapse. |
|---|---|
| Authors: | Guzikowski, Natalie J., Kavalali, Ege T. |
| Source: | Nature Communications; 11/21/2024, Vol. 14 Issue 1, p1-14, 14p |
| Abstract: | The mechanisms that enable synapses to achieve temporally and spatially precise signaling at nano-scale while being fluid with the cytosol are poorly understood. Liquid-liquid phase separation (LLPS) is emerging as a key principle governing subcellular organization; however, the impact of synaptic LLPS on neurotransmission is unclear. Here, using rat primary hippocampal cultures, we show that robust disruption of neuronal LLPS with aliphatic alcohols severely dysregulates action potential-dependent neurotransmission, while spontaneous neurotransmission persists. Synaptic LLPS maintains synaptic vesicle pool clustering and recycling as well as the precise organization of active zone RIM1/2 and Munc13 nanoclusters, thus supporting fast evoked Ca2+-dependent release. These results indicate although LLPS is necessary within the nanodomain of the synapse, the disruption of this nano-organization largely spares spontaneous neurotransmission. Therefore, properties of in vitro micron sized liquid condensates translate to the nano-structure of the synapse in a functionally specific manner regulating action potential-evoked release.In this study, Guzikowski and Kavalali find properties of in vitro micron sized liquid condensates translate to the nano-structure of the synapse in a functionally specific manner, creating a distinct nano-organization that facilitates subsequent synaptic signaling. [ABSTRACT FROM AUTHOR] |
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| Database: | Complementary Index |
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| Items | – Name: Title Label: Title Group: Ti Data: Functional specificity of liquid-liquid phase separation at the synapse. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Guzikowski%2C+Natalie+J%2E%22">Guzikowski, Natalie J.</searchLink><br /><searchLink fieldCode="AR" term="%22Kavalali%2C+Ege+T%2E%22">Kavalali, Ege T.</searchLink> – Name: TitleSource Label: Source Group: Src Data: Nature Communications; 11/21/2024, Vol. 14 Issue 1, p1-14, 14p – Name: Abstract Label: Abstract Group: Ab Data: The mechanisms that enable synapses to achieve temporally and spatially precise signaling at nano-scale while being fluid with the cytosol are poorly understood. Liquid-liquid phase separation (LLPS) is emerging as a key principle governing subcellular organization; however, the impact of synaptic LLPS on neurotransmission is unclear. Here, using rat primary hippocampal cultures, we show that robust disruption of neuronal LLPS with aliphatic alcohols severely dysregulates action potential-dependent neurotransmission, while spontaneous neurotransmission persists. Synaptic LLPS maintains synaptic vesicle pool clustering and recycling as well as the precise organization of active zone RIM1/2 and Munc13 nanoclusters, thus supporting fast evoked Ca<superscript>2+</superscript>-dependent release. These results indicate although LLPS is necessary within the nanodomain of the synapse, the disruption of this nano-organization largely spares spontaneous neurotransmission. Therefore, properties of in vitro micron sized liquid condensates translate to the nano-structure of the synapse in a functionally specific manner regulating action potential-evoked release.In this study, Guzikowski and Kavalali find properties of in vitro micron sized liquid condensates translate to the nano-structure of the synapse in a functionally specific manner, creating a distinct nano-organization that facilitates subsequent synaptic signaling. [ABSTRACT FROM AUTHOR] – Name: Abstract Label: Group: Ab Data: <i>Copyright of Nature Communications is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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