A role for prenylated rab acceptor 1 in vertebrate photoreceptor development

BMC Neuroscience

Judith Mosinger Ogilvie⁷  Anand Swaroop³  Adnan Y Chowdhury⁶  Alan J Mears⁴  Ritu Khanna¹  Mohammed I Othman¹  Matthew J Brooks³  Sean CE Hoge⁵  Joshua G Martak⁵  Ameair Abu Irqeba⁷  Angela M Richmond⁸  Virginia M Dickison² 

[1] Department of Ophthalmology and Visual Sciences, W.K. Kellogg Eye Center, University of Michigan, Ann Arbor, MI, USA;Current address: Southern Illinois University Edwardsville, School of Pharmacy, Edwardsville, IL, USA;Neurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA;Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada;Current address: Saint Louis University School of Medicine, St. Louis, Missouri, USA;Current address: Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri, USA;Department of Biology, Saint Louis University, St. Louis, Missouri, USA;Current address: Washington University in St. Louis School Of Medicine, St. Louis, Missouri, USA

关键词: Vesicular trafficking;    Rab6;    Prenylated Rab Acceptor 1;    Rabac1;    Photoreceptor development;    Retinal degeneration;    Mouse;    Photoreceptor;    Retina;   

Others  :  1140691
DOI  :  10.1186/1471-2202-13-152

 received in 2012-06-18, accepted in 2012-11-19,  发布年份 2012

【 摘 要 】

Background

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2012 Dickison et al.; licensee BioMed Central Ltd.

【 图 表 】

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