Identification of an outer segment targeting signal in the COOH terminus of rhodopsin using transgenic Xenopus laevis.
Identification of an outer segment targeting signal in the COOH terminus of rhodopsin using transgenic Xenopus laevis.
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DOI：
10.1083/jcb.151.7.1369
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发表时间：
2000-12-25
期刊：
影响因子：
--
通讯作者：
Papermaster DS
中科院分区：
文献类型：
--
作者：
Tam BM;Moritz OL;Hurd LB;Papermaster DS
某些遗传性视网膜退行性疾病可能与光色素视紫红质定位错误有关。在此，我们阐明了视紫红质的靶向信号，该信号负责其向杆外段（ROS）的极化分布。在非洲爪蟾视蛋白启动子的调控下，多种绿色荧光蛋白(GFP)/视紫红质cooh末端融合蛋白在转基因非洲爪蟾的主要红杆光感受器中特异性表达。融合蛋白通过脂质修饰（棕榈酰化和肉豆蔻酰化）靶向膜，而不是膜跨越结构域。膜结合被发现是必要的，但不是有效的ROS定位的充分条件。一种仅含有非洲爪蟾视紫质胞质cooh末端44个氨基酸的GFP融合蛋白，该蛋白仅定位于ROS膜上。视紫红质与α肾上腺素能受体cooh末端序列的嵌合进一步将视紫红质的ROS定位信号细化到远端8个氨基酸。该区域的突变/缺失导致融合蛋白部分离域到棒内段（RIS）膜。内源性野生型视紫质的靶向和运输不受错定位GFP融合蛋白存在的影响。
Mislocalization of the photopigment rhodopsin may be involved in the pathology of certain inherited retinal degenerative diseases. Here, we have elucidated rhodopsin's targeting signal which is responsible for its polarized distribution to the rod outer segment (ROS). Various green fluorescent protein (GFP)/rhodopsin COOH-terminal fusion proteins were expressed specifically in the major red rod photoreceptors of transgenic Xenopus laevis under the control of the Xenopus opsin promoter. The fusion proteins were targeted to membranes via lipid modifications (palmitoylation and myristoylation) as opposed to membrane spanning domains. Membrane association was found to be necessary but not sufficient for efficient ROS localization. A GFP fusion protein containing only the cytoplasmic COOH-terminal 44 amino acids of Xenopus rhodopsin localized exclusively to ROS membranes. Chimeras between rhodopsin and α adrenergic receptor COOH-terminal sequences further refined rhodopsin's ROS localization signal to its distal eight amino acids. Mutations/deletions of this region resulted in partial delocalization of the fusion proteins to rod inner segment (RIS) membranes. The targeting and transport of endogenous wild-type rhodopsin was unaffected by the presence of mislocalized GFP fusion proteins.
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DOI：
10.1073/pnas.95.18.10620
发表时间：
1998-09-01
影响因子：
11.1
作者：
Deretic, D;Schmerl, S;McDowell, JH
通讯作者：
McDowell, JH
影响因子：
4.8
作者：
Batni, S;Scalzetti, L;Knox, BE
通讯作者：
Knox, BE
影响因子：
64.5
作者：
DOTTI, CG;SIMONS, K
通讯作者：
SIMONS, K
DOI：
10.1083/jcb.103.5.1767
发表时间：
1986-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fuller SD;Simons K
通讯作者：
Simons K
影响因子：
7.8
作者：
BESHARSE, JC;PFENNINGER, KH
通讯作者：
PFENNINGER, KH