Uncoupling of photoreceptor peripherin/rds fusogenic activity from biosynthesis, subunit assembly, and targeting: a potential mechanism for pathogenic effects

The Journal of Biological Chemistry
Linda M RitterAndrew F X Goldberg

Abstract

Inherited defects in the RDS gene cause a multiplicity of progressive retinal diseases in humans. The gene product, peripherin/rds (P/rds), is a member of the tetraspanin protein family required for normal vertebrate photoreceptor outer segment (OS) architecture. Although its molecular function remains uncertain, P/rds has been suggested to catalyze membrane fusion events required for the OS renewal process. This study investigates the importance of two charged residues within a predicted C-terminal helical region for protein biosynthesis, localization, and interaction with model membranes. Targeted mutagenesis was utilized to neutralize charges at Glu(321) and Lys(324) individually and in combination to generate three mutant variants. Studies were conducted on variants expressed as 1) full-length P/rds in COS-1 cells, 2) glutathione S-transferase fusion proteins in Escherichia coli, and 3) membrane-associated green fluorescent protein fusion proteins in transgenic Xenopus laevis. None of the mutations affected biosynthesis of full-length P/rds in COS-1 cells as assessed by Western blotting, sedimentation velocity, and immunofluorescence microscopy. Although all mutations reside within a recently identified localization signal,...Continue Reading

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Citations

Sep 3, 2008·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Arne M NystuenNeena B Haider
Aug 5, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Linda M RitterAndrew F X Goldberg
Apr 6, 2006·The Journal of Cell Biology·Rafal FarjoMuna I Naash
Mar 11, 2008·Progress in Retinal and Eye Research·Camiel J F BoonJan E E Keunen
Nov 14, 2006·International Review of Cytology·Andrew F X Goldberg
Dec 7, 2006·Ophthalmic Genetics·Rafal Farjo, Muna I Naash
Dec 14, 2004·The Journal of Biological Chemistry·Monika Damek-PoprawaKathleen Boesze-Battaglia

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