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J Biol Chem, Vol. 275, Issue 18, 13191-13194, May 5, 2000

ACCELERATED PUBLICATION
Peripherin/rds Influences Membrane Vesicle Morphology
IMPLICATIONS FOR RETINOPATHIES^*

Jonathan D. J. Wrigley, Tanweer Ahmed, Claire L. Nevett, and John B. C. Findlay^§

From the School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom

Peripherin/rds is an integral membrane glycoprotein found in the rim regions of vertebrate photoreceptor cell discs. Natural mutations of the encoding gene result in degenerative retinal disorders, such as retinitis pigmentosa. The retinal degeneration slow (rds) phenotype, observed in mice, is considered to be an appropriate model for peripherin/rds-mediated retinitis pigmentosa. Associated abnormalities in the outer segment of photoreceptor cells have implicated peripherin/rds in some aspect of disc morphology, yet it remains unclear whether such morphological effects are the cause or the result of this condition. Here we present the first direct evidence to support a role for peripherin/rds in maintaining the flattened vesicle morphology characteristic of photoreceptor outer segments. In vitro expression yields a 36-kDa immunoreactive species, which is inserted into membranes and undergoes N-glycosylation, inter- and intramolecular disulfide bonding, and dimerization. Electron microscopy reveals that peripherin/rds flattens microsomal vesicles. This effect appears to be dependent on disulfide bond formation but not N-glycosylation. The inability of two pathogenic peripherin/rds mutants (P216L and C165Y) to flatten membrane vesicles implicates such mutations as the primary cause of the retinal degeneration observed in retinitis pigmentosa.

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^* 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.

Recipient of a studentship for this work from the "Fight for Sight" charity, London, United Kingdom.

^§ To whom correspondence should be addressed. Tel.: 44-113-2333140; Fax: 44-113-2333167; E-mail: j.b.c.findlay@leeds.ac.uk.

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Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

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