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bioRxiv · 10.1101/2024.12.19.629437

Segregated localization of target-SNARE proteins within presynaptic terminals of Munc18-1 deficient photoreceptors

Huang, M.·Chow, C. H.·Charish, J.·Indrawinata, K.·Harada, H.·Wallace, V. A.·Monnier, P. P.·Sugita, S.
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Abstract

Sec1/Munc18 family proteins are essential for SNARE-mediated vesicular exocytosis. However, where SNARE proteins are localized in Munc18-1 deficient presynaptic terminals remains unclear due to the rapid degeneration of neurons lacking Munc18-1. Here, we found that removing Munc18-1 from photoreceptor cells did not result in major cellular loss until postnatal day 14, which allowed us to investigate the role of Munc18-1 in endogenous presynaptic terminals. In the absence of Munc18-1, even before major photoreceptor cell degeneration, functional impairments were present. While Munc18-1 was not required for the pre-synaptic enrichment of the t-SNARE proteins syntaxin-3 and SNAP-25, it played a critical role in their proper localization. In wild-type conditions, t-SNAREs are highly colocalized. However, in the absence of Munc18-1, their distribution becomes strikingly segregated. Immuno-electron microscopy revealed that without Munc18-1, syntaxin-3 is retained within various organelle membranes rather than being targeted to synaptic plasma membranes. These findings provide the first evidence that Munc18-1 is important to prevent segregation of syntaxin-3 and SNAP-25 within presynaptic terminals.

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Huang, M., Chow, C. H., Charish, J., Indrawinata, K., Harada, H., Wallace, V. A., Monnier, P. P., Sugita, S.. 2024-12-20. Segregated localization of target-SNARE proteins within presynaptic terminals of Munc18-1 deficient photoreceptors. https://doi.org/10.1101/2024.12.19.629437

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