SARA-regulated vesicular targeting underlies formation of the Light-Sensing organelle in mammalian rods
SARA-regulated vesicular targeting underlies formation of the Light-Sensing organelle in mammalian rods
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DOI：
10.1016/j.cell.2007.06.030
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发表时间：
2007-08-10
期刊：
影响因子：
64.5
通讯作者：
Sung, Ching-Hwa
中科院分区：
文献类型：
--
作者：
Chuang, Jen-Zen;Zhao, Yu;Sung, Ching-Hwa
脊椎动物视杆感光细胞的感光细胞器，即外节 (OS)，是一种经过修饰的纤毛，含有类似于 1,000 个堆叠的圆盘膜，这些圆盘膜密集地填充有视觉色素视紫红质。哺乳动物操作系统每十天更新一次；新光盘是通过一种不太了解的机制在操作系统的基础上组装的。我们的结果表明，椎间盘的形成和成熟过程涉及特定的磷脂定向的囊泡膜靶向。 OS 轴丝细胞质中充满视紫红质的囊泡与新生椎间盘融合，新生椎间盘高度特化，富含丰富的磷脂酰肌醇 3-磷酸 (PI3P)。这种膜耦合由包含 FYVE 结构域的蛋白 SARA 通过其与 PI3P、视紫红质和 SNARE 蛋白突触蛋白 3 的直接相互作用来调节。我们的模型与之前提出的外翻模型相反，表明操作系统中视紫红质的囊泡递送将视紫红质浓缩到椎间盘中，并且该过程直接参与椎间盘的生物发生。
The light-sensing organelle of the vertebrate rod photoreceptor, the outer segment (OS), is a modified cilium containing similar to 1,000 stacked disc membranes that are densely packed with visual pigment rhodopsin. The mammalian OS is renewed every ten days; new discs are assembled at the base of the OS by a poorly understood mechanism. Our results suggest that discs are formed and matured in a process that involves specific phospholipid-directed vesicular membrane targeting. Rhodopsin-laden vesicles in the OS axonemal cytoplasm fuse with nascent discs that are highly specialized with abundant phosphatidylinositol 3-phosphate (PI3P). This membrane coupling is regulated by the FYVE domain-containing protein, SARA, through its direct interaction with PI3P, rhodopsin, and SNARE protein syntaxin 3. Our model, in contrast to the previously proposed evagination model, suggests that the vesicular delivery of rhodopsin in the OS concentrates rhodopsin into discs, and this process directly participates in disc biogenesis.