The BH3-Only SNARE BNip1 Mediates Photoreceptor Apoptosis in Response to Vesicular Fusion Defects

• β-SNAP mutation causes BNip1-dependent apoptosis in zebrafish photoreceptors
• BNip1 apoptotic pathway is activated by the syntaxin-18 cis-SNARE complex
• BNip1 promotes Bax-mediated apoptosis in a BH3-domain-dependent manner
• β-SNAP inhibits apoptosis by disassembling the syntaxin-18 cis-SNARE complex

SummaryIntracellular vesicular transport is important for photoreceptor function and maintenance. However, the mechanism underlying photoreceptor degeneration in response to vesicular transport defects is unknown. Here, we report that photoreceptors undergo apoptosis in a zebrafish β-soluble N-ethylmaleimide-sensitive factor attachment protein (β-SNAP) mutant. β-SNAP cooperates with N-ethylmaleimide-sensitive factor to recycle the SNAP receptor (SNARE), a key component of the membrane fusion machinery, by disassembling the cis-SNARE complex generated in the vesicular fusion process. We found that photoreceptor apoptosis in the β-SNAP mutant was dependent on the BH3-only protein BNip1. BNip1 functions as a component of the syntaxin-18 SNARE complex and regulates retrograde transport from the Golgi to the endoplasmic reticulum. Failure to disassemble the syntaxin-18 cis-SNARE complex caused BNip1-dependent apoptosis. These data suggest that the syntaxin-18 cis-SNARE complex functions as an alarm factor that monitors vesicular fusion competence and that BNip1 transforms vesicular fusion defects into photoreceptor apoptosis.

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