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

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.