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<p>The function of the SNARE complex regulator, Munc18-1, in photoreceptor cells is unknown. Here, we found that removing Munc18-1 from photoreceptors results in major degeneration starting at P14. In the absence of Munc18-1, before major photoreceptor degeneration, functional and synaptic impairments were present, indicating a critical function of Munc18-1. Furthermore, Munc18-1 played a critical role in expression and localization of syntaxin-3. The syntaxin-3 protein level is dramatically reduced in the soma and plasma membrane of photoreceptors without Munc18-1. At the photoreceptor synapses, the colocalization of syntaxin-3 and its SNARE partner, SNAP-25, was reduced, potentially suggesting an altered syntaxin-3 synaptic localization. In the Munc18-1-deficient photoreceptors, immature synapses and outer segment lesions were found. Taken together, these findings provide evidence that Munc18-1 is important for maintaining sufficient syntaxin-3 expression in the cell body and synapses of photoreceptors. The lack of Munc18-1, combined with poor syntaxin-3 expression, contributes to photoreceptor functional impairment and degeneration.</p>

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Munc18-1 is crucial for photoreceptor function, survival and regulation of syntaxin-3 localization and expression

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月4日

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  • Mengjia Huang,
  • Chun Hin Chow,
  • Ryan Noworolski,
  • Jason Charish,
  • Karen Indrawinata,
  • Hidekiyo Harada,
  • Valerie A. Wallace,
  • Philippe P. Monnier,
  • Shuzo Sugita

摘要

The function of the SNARE complex regulator, Munc18-1, in photoreceptor cells is unknown. Here, we found that removing Munc18-1 from photoreceptors results in major degeneration starting at P14. In the absence of Munc18-1, before major photoreceptor degeneration, functional and synaptic impairments were present, indicating a critical function of Munc18-1. Furthermore, Munc18-1 played a critical role in expression and localization of syntaxin-3. The syntaxin-3 protein level is dramatically reduced in the soma and plasma membrane of photoreceptors without Munc18-1. At the photoreceptor synapses, the colocalization of syntaxin-3 and its SNARE partner, SNAP-25, was reduced, potentially suggesting an altered syntaxin-3 synaptic localization. In the Munc18-1-deficient photoreceptors, immature synapses and outer segment lesions were found. Taken together, these findings provide evidence that Munc18-1 is important for maintaining sufficient syntaxin-3 expression in the cell body and synapses of photoreceptors. The lack of Munc18-1, combined with poor syntaxin-3 expression, contributes to photoreceptor functional impairment and degeneration.