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Roser Gonzalez-Duarte, Rosa Andrés, Elena B. Domenech, Alejandro Garanto, Mariona Esquerdo, Florentina Sava, Muna I Naash, Gemma Marfany; CERKL isoforms are differentially expressed in retinal cells. Invest. Ophthalmol. Vis. Sci. 2017;58(8):596.
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© ARVO (1962-2015); The Authors (2016-present)
CERKL mutations cause retinitis pigmentosa and cone-rod dystrophy in human. The CERKL gene is a paradigm for high transcriptional complexity, with many isoforms produced by alternative splicing and the use of alternative promoters. Besides, the protein comprises among other several domains, lipid kinase, nuclear localization and nuclear export signals. Although the precise physiological function is still unknown, CERKL overexpression protects cells from apoptosis triggered by oxidative stress.
We have performed immunochemistry detection studies on retinal sections of wild-type, Cerkl knockdown and Nrl knockout mice, as well as in primary retinal cell cultures (retinal ganglion cells, rods and cones) in normal and under oxidative stress conditions, using a panel of several in-house made antibodies against different CERKL domains. Differential CERKL mRNA and protein isoform expression in rods and cones have been assessed by immunodetection and RT-PCR on enriched population of specific cell-types.
In vitro studies showed that CERKL binds mRNA and contributes to stress granule complexes. These in vitro results have been further confirmed in isolated retinal neurons (retinal ganglion cells and photoreceptors), where CERKL co-localizes with RNA and RNA-binding proteins and is a component of the stress granules produced under oxidative-stress conditions. Moreover, differential localization of CERKL isoforms in rods and cones has been shown using a panel of in-house antibodies and analysis of mRNA expression by RT-PCR.
This differential isoform specifity is highly suggestive of specific functional roles for CERKL in different photoreceptor cell types. Future work will address the impact of CERKL mutations in rods and cones related to human visual pathophysiology.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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