Journal of Biological Chemistry
Volume 275, Issue 32, 11 August 2000, Pages 24752-24759
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PROTEIN SYNTHESIS POST-TRANSLATION MODIFICATION AND DEGRADATION
Role of Asparagine-linked Oligosaccharides in Rhodopsin Maturation and Association with Its Molecular Chaperone, NinaA*

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Many proteins require N-linked glycosylation for conformational maturation and interaction with their molecular chaperones. In Drosophila, rhodopsin (Rh1), the most abundant rhodopsin, is glycosylated in the endoplasmic reticulum (ER) and requires its molecular chaperone, NinaA, for exit from the ER and transport through the secretory pathway. Studies of vertebrate rhodopsins have generated several conflicting proposals regarding the role of glycosylation in rhodopsin maturation. We investigated the role of Rh1 glycosylation and Rh1/NinaA interactions under in vivo conditions by analyzing transgenic flies expressing Rh1 with isoleucine substitutions at each of the two consensus sites forN-linked glycosylation (N20I and N196I). We show that Asn20 is the sole site for glycosylation. The Rh1N20I protein is retained within the secretory pathway, causing an accumulation of ER cisternae and dilation of the Golgi complex. NinaA associates with nonglycosylated Rh1N20I; therefore, retention of nonglycosylated rhodopsin within the ER is not due to the lack of Rh1N20I/NinaA interaction. We further show that Rh1N20I interferes with wild type Rh1 maturation and triggers a dominant form of retinal degeneration. We conclude that during maturation Rh1 is present in protein complexes containing NinaA and that Rh1 glycosylation is required for transport of the complexes through the secretory pathway. Failure of this transport process leads to retinal degeneration.

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Published, JBC Papers in Press, May 15, 2000, DOI 10.1074/jbc.M002668200

*

This work was supported by National Institutes of Health Grant EY08768, by the Retina Research Foundation, the Howard Hughes Medical Institute, the Foundation Fighting Blindness, Fight-For-Sight, and the Research to Prevent Blindness foundation (to N. J. C.), and by National Institutes of Health Grant EY06808 (to J. E. O.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.