Adaptation of pineal expressed teleost exo-rod opsin to non-image forming photoreception through enhanced Meta II decay.
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ABSTRACT:
SUBMITTER: Tarttelin EE
PROVIDER: S-EPMC3203999 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeMisfolding mutations in rod opsin are a major cause of the inherited blindness retinitis pigmentosa. Therefore, understanding the role of molecular chaperones in facilitating rod opsin biogenesis and the response to mutant rod opsin is important for retinal disease and fundamental retinal cell biology. A recent report has shown that Drosophila rhodopsin Rh1 requires calnexin (Cnx) for its maturation and correct localization to R1-6 rhabdomeres. In this report, we investigate the role of Cnx in the processing of wild-type and mutant mammalian rod opsin.MethodsMouse embryonic fibroblasts (MEFs) from control mice (WT) and mice that express a truncated dysfunctional version of Cnx (sCnx) were used to assess the role of Cnx in the biogenesis, maturation, degradation, and aggregation of mutant and wild-type rod opsin. The mutant P23H rod opsin was used as a prototypical class II misfolding mutant as it is retained in the endoplasmic reticulum (ER) and is either degraded by ER associated degradation (ERAD) or forms aggregates that coalesce to form intracellular inclusions.ResultsWild-type rod opsin protein translocated normally to the plasma membrane in both cell lines. In contrast, P23H rod opsin was retained in the ER in both cell lines. The only difference observed in rod opsin processing between the WT and sCnx MEFs was a small increase in the incidence of P23H intracellular inclusions in the sCnx cells. This did not appear to be specific for rod opsin, however, as non-rod opsin-expressing sCnx cells also had an increased incidence of ubiquitylated inclusions.ConclusionsOur data show that, unlike Drosophila Rh1, mammalian rod opsin biogenesis does not appear to have an absolute requirement for Cnx. Other chaperones are likely to be more important for mammalian rod opsin biogenesis and quality control.
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