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Xianjun Zhu, Lin Zhang; Deletion of ER complex protein Emc3 led to photoreceptor degeneration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):994.
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© ARVO (1962-2015); The Authors (2016-present)
In eukaryotic cells, integral membrane proteins are synthesized folded in the endoplasmic reticulum (ER) and transported to their destination. During this process, multiple chaperones and folding enzymes are required for the folding of the integral membrane proteins in the ER. In the retina photoreceptors, biosynthesis and folding of rhodopsin requires molecular chaperones in the ER. ER membrane protein complex (EMC) proteins played important roles in Drosophila rhodopsin transport. In mammals, EMC3 is localized to the outer segment and inner segment of photoreceptor cells, similar to Rho. However, its roles remain elusive. We set out to investigate the role of Emc3 in the mouse retina.
All animal study protocols were approved by the local ethics committee and followed the guideline of the Use of Animals in Ophthalmic and Visual Research of ARVO. Conditional knockout mice for Emc3 in the cones and rods were generated to assess its in vivo functions. Scotopic and photopic electroretinograms were recorded for wild-type (WT) and knockout (KO) mice to evaluate the function of rods and cones in the retina. Histological study was carried out to assess the cell loss in outer nuclear layer (ONL). Immunofluorescence staining was performed on WT and KO retina to reveal pathological alterations caused by Emc3 deficiency.
Deletion of Emc3 in cones led to reduced photopic ERG response and rapid degeneration of cone cells. Immunostaining study revealed that cone opsins were mislocalized to the inner segment and cell body, compared to wildtype controls. Similarly, deletion of Emc3 in rods resulted in reduced rhodopsin expression and mislocaliztion of rhodopsin to the cell body. Outer segment became shorter in the mutant mice.
Our data demonstrated that Emc3 is essential for proper maintenance of retinal structure and function.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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