A role for prenylated rab acceptor 1 in vertebrate photoreceptor development.

A role for prenylated rab acceptor 1 in vertebrate photoreceptor development.
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DOI:
10.1186/1471-2202-13-152
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发表时间:
2012-12-15
期刊:
影响因子:
2.4
通讯作者:
Ogilvie JM
Ogilvie JM
中科院分区:
医学4区
文献类型:
--
作者:
Dickison VM;Richmond AM;Abu Irqeba A;Martak JG;Hoge SC;Brooks MJ;Othman MI;Khanna R;Mears AJ;Chowdhury AY;Swaroop A;Ogilvie JM

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rd 1小鼠视网膜是视网膜变性的充分研究模型,其中杆光感受器在出生后第10天(P)开始经历细胞死亡,直到P21。这一时期与正常视网膜中的感光细胞终末分化相一致。我们已经使用rd 1视网膜作为模型,以研究早期分子缺陷,在发展杆光感受器开始变性之前。使用微阵列的方法,我们进行了基因分析比较rd 1和野生型(wt)视网膜在四个时间点开始于P2,在任何明显的生化或形态学差异,并在P8结束,开始细胞死亡之前。在143个鉴定的差异表达基因中,我们集中在Rab受体1(Rabac 1),其编码蛋白质Prenylated rab受体1(PRA 1),并在囊泡运输中起重要作用。定量RT-PCR分析证实在所有检查的时间点,在rd 1视网膜中PRA 1的表达减少。免疫组化结果显示,在野生型视网膜感光细胞分化过程中,随着高尔基体从核周体向内节移位,PRA 1样免疫反应(LIR)与顺式高尔基体标记GM-130共定位于感光细胞中。弥漫性PRA 1-LIR,不同于高尔基体标记物,在P8开始的野生型光感受器的远端内段中观察到。在出生后发育过程中,两个丛状层都含有独立于GM-130染色的PRA 1阳性斑点。在视网膜内层,PRA 1-LIR也与高尔基体标记物共定位在大多数细胞的核周区域。在rd 1小鼠的内层视网膜中也观察到类似的模式。然而,点状和显着减少PRA 1-LIR是目前整个发展中的rd 1内段,延迟感光细胞的发展和异常高尔基体分类和囊泡贩运一致。我们已经确定了在早期时间点在rd 1视网膜中差异调节的基因,这可能会使感光细胞死亡之前的发育缺陷的见解。这是首次报道PRA 1在视网膜中的表达。我们的数据支持这一假设,PRA 1在高尔基体和纤毛之间的小泡运输分化和成熟杆光感受器中起着重要作用。
The rd1 mouse retina is a well-studied model of retinal degeneration where rod photoreceptors undergo cell death beginning at postnatal day (P) 10 until P21. This period coincides with photoreceptor terminal differentiation in a normal retina. We have used the rd1 retina as a model to investigate early molecular defects in developing rod photoreceptors prior to the onset of degeneration. Using a microarray approach, we performed gene profiling comparing rd1 and wild type (wt) retinas at four time points starting at P2, prior to any obvious biochemical or morphological differences, and concluding at P8, prior to the initiation of cell death. Of the 143 identified differentially expressed genes, we focused on Rab acceptor 1 (Rabac1), which codes for the protein Prenylated rab acceptor 1 (PRA1) and plays an important role in vesicular trafficking. Quantitative RT-PCR analysis confirmed reduced expression of PRA1 in rd1 retina at all time points examined. Immunohistochemical observation showed that PRA1-like immunoreactivity (LIR) co-localized with the cis-Golgi marker GM-130 in the photoreceptor as the Golgi translocated from the perikarya to the inner segment during photoreceptor differentiation in wt retinas. Diffuse PRA1-LIR, distinct from the Golgi marker, was seen in the distal inner segment of wt photoreceptors starting at P8. Both plexiform layers contained PRA1 positive punctae independent of GM-130 staining during postnatal development. In the inner retina, PRA1-LIR also colocalized with the Golgi marker in the perinuclear region of most cells. A similar pattern was seen in the rd1 mouse inner retina. However, punctate and significantly reduced PRA1-LIR was present throughout the developing rd1 inner segment, consistent with delayed photoreceptor development and abnormalities in Golgi sorting and vesicular trafficking. We have identified genes that are differentially regulated in the rd1 retina at early time points, which may give insights into developmental defects that precede photoreceptor cell death. This is the first report of PRA1 expression in the retina. Our data support the hypothesis that PRA1 plays an important role in vesicular trafficking between the Golgi and cilia in differentiating and mature rod photoreceptors.
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