Autor: |
Wrigley, Jonathan D.J., Ahmed, Tanweer, Nevett, Claire L., Findlay, John B.C. |
Zdroj: |
Journal of Biological Chemistry; May 2000, Vol. 275 Issue: 18 p13191-13194, 4p |
Abstrakt: |
Peripherin/rdsis 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/rdsin 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/rdsin maintaining the flattened vesicle morphology characteristic of photoreceptor outer segments. In vitroexpression 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/rdsflattens microsomal vesicles. This effect appears to be dependent on disulfide bond formation but notN-glycosylation. The inability of two pathogenic peripherin/rdsmutants (P216L and C165Y) to flatten membrane vesicles implicates such mutations as the primary cause of the retinal degeneration observed in retinitis pigmentosa. |
Databáze: |
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