The BH3-Only SNARE BNip1 Mediates Photoreceptor Apoptosis in Response to Vesicular Fusion Defects
The BH3-Only SNARE BNip1 Mediates Photoreceptor Apoptosis in Response to Vesicular Fusion Defects
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DOI：
10.1016/j.devcel.2013.04.015
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发表时间：
2013-05-28
影响因子：
11.8
通讯作者：
Masai, Ichiro
中科院分区：
文献类型：
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作者：
Nishiwaki, Yuko;Yoshizawa, Asuka;Masai, Ichiro
胞内囊泡转运对于光感受器的功能和维持是重要的。然而，囊泡运输缺陷引起的感光细胞变性的机制尚不清楚。在这里，我们报告说，光感受器在斑马鱼β-可溶性N-乙基-马来酰亚胺敏感因子附着蛋白（β-SNAP）突变体进行细胞凋亡。β-SNAP与N-乙基-马来酰亚胺敏感因子合作，通过分解囊泡融合过程中产生的顺式SNARE复合物来回收SNAP受体（SNARE），SNARE是膜融合机制的关键组分。我们发现，感光细胞凋亡的β-SNAP突变体是依赖于BH 3-唯一的蛋白质BNip 1。BNip 1作为syntaxin-18 SNARE复合物的一个组成部分发挥作用，并调节从高尔基体到内质网的逆行转运。未能分解syntaxin-18顺式SNARE复合物导致BNip 1依赖性细胞凋亡。这些数据表明，syntaxin-18顺式SNARE复合物的功能作为一个报警因子，监测囊泡融合能力和BNip 1转换囊泡融合缺陷感光细胞凋亡。
Intracellular 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 beta-soluble N-ethyl-maleimide-sensitive factor attachment protein (beta-SNAP) mutant. beta-SNAP cooperates with N-ethyl-maleimide-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 beta-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.