Rhodopsin C terminus, the site of mutations causing retinal disease, regulates trafficking by binding to ADP-ribosylation factor 4 (ARF4)
Rhodopsin C terminus, the site of mutations causing retinal disease, regulates trafficking by binding to ADP-ribosylation factor 4 (ARF4)
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DOI：
10.1073/pnas.0500095102
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发表时间：
2005-03-01
影响因子：
11.1
通讯作者：
Arendt, A
中科院分区：
文献类型：
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作者：
Deretic, D;Williams, AH;Arendt, A
视紫红质突变导致人类常染色体显性视网膜色素变性，从而损害感光细胞极性的维持。严重形式的突变发生在视紫红质的C末端分选信号VXPX-COOH中。在这里，我们报告说，这种排序基序结合特异性的小GTdR ARF 4，ARF家族的膜出芽和蛋白质分选调节剂的成员。阻断ARF 4作用的效果在功能上等同于阻断视紫红质C-末端分选信号的效果。ARF 4是产生后高尔基载体针对视网膜光感受器的杆外节是必不可少的。因此，影响视紫红质分选信号的严重视网膜色素变性等位基因干扰ARF 4和视紫红质之间的相互作用，导致异常运输和视网膜变性的开始。
The maintenance of photoreceptor cell polarity is compromised by the rhodopsin mutations causing the human disease autosomal dominant retinitis pigmentosa. The severe form mutations occur in the C-terminal sorting signal of rhodopsin, VXPX-COOH. Here, we report that this sorting motif binds specifically to the small GTPase ARF4, a member of the ARF family of membrane budding and protein sorting regulators. The effects of blocking ARF4 action were functionally equivalent to the effects of blocking the rhodopsin C-terminal sorting signal. ARF4 was essential for the generation of post-Golgi carriers targeted to the rod outer segments of retinal photoreceptors. Thus, the severe retinitis pigmentosa alleles that affect the rhodopsin sorting signal interfere with interactions between ARF4 and rhodopsin, leading to aberrant trafficking and initiation of retinal degeneration.