GC1 deletion prevents light-dependent arrestin translocation in mouse cone photoreceptor cells

GC1 deletion prevents light-dependent arrestin translocation in mouse cone photoreceptor cells
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DOI:
10.1167/iovs.04-0691
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发表时间:
2005-01-01
影响因子:
4.4
通讯作者:
Semple-Rowland, SL
Semple-Rowland, SL
中科院分区:
医学2区
文献类型:
--
作者:
Coleman, JE;Semple-Rowland, SL

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目的。光导调节蛋白在光感受器细胞内外段之间的光驱动易位在这些细胞对光的适应中起作用。本研究的目的是研究鸟苷酸环化酶1 (GC1)缺失对杆状和锥状细胞中光驱动蛋白易位的影响。两种细胞都表达GC1,但在灵敏度、饱和度和对光的响应时间上有所不同。采用针对锥体和杆状转导蛋白α (Talpha)亚基和抑制蛋白特异性抗体的免疫组织化学技术,研究了野生型和GC1敲除(KO)小鼠视网膜中这些蛋白的光驱动易位。在GC1缺失的情况下,从锥体外节到细胞内区域的锥体阻滞蛋白的转运被破坏,而杆状体中阻滞蛋白和Talpha的转运不受影响。在野生型和GC1型小鼠视网膜中,锥α未发生移位,但其在GC1型小鼠视网膜中的亚细胞分布不同,在光照和黑暗条件下均停留在锥外段。这些结果表明,多种独立的途径调节光转导蛋白的易位,GC1,可能还有cGMP,在锥体阻滞蛋白易位的信号传导中起着关键作用。
PURPOSE. Light-driven translocation of phototransduction regulatory proteins between the inner and outer segments of photoreceptor cells plays a role in the adaptation of these cells to light. The purpose of this study was to examine the effects of the absence of guanylate cyclase 1 (GC1) on light-driven protein translocation in rod and cone cells. Both cell types express GC1, but differ in sensitivity, saturation, and response times to light.METHODS. Immunohistochemical techniques employing antibodies specific for cone and rod transducin alpha (Talpha) subunits and arrestins were used to examine light-driven translocation of these proteins in the retinas of wild-type and GC1 knockout ( KO) mice.RESULTS. Translocation of cone arrestin from cone outer segments to the inner cell regions was disrupted in the absence of GC1, whereas translocation of arrestin and Talpha in rods was not affected. Cone Talpha did not translocate in wild-type and GC1 KO mice, but differed in its subcellular distribution in GC1 KO retina, remaining in the cone outer segment in light and in dark.CONCLUSIONS. These results suggest that multiple, independent pathways regulate the translocation of phototransduction proteins and that GC1, and presumably cGMP, are of key importance in signaling the translocation of cone arrestin.