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A single valine residue plays an essential role in peripherin/rds targeting to photoreceptor outer segments
Journal article   Open access   Peer reviewed

A single valine residue plays an essential role in peripherin/rds targeting to photoreceptor outer segments

Raquel Y Salinas, Sheila A Baker, Sidney M Gospe III and Vadim Y Arshavsky
PloS one, Vol.8(1), pp.e54292-e54292
2013
DOI: 10.1371/journal.pone.0054292
PMCID: PMC3544770
PMID: 23342122
url
https://doi.org/10.1371/journal.pone.0054292View
Published (Version of record) Open Access

Abstract

Peripherin/retinal degeneration slow (rds) is an integral membrane protein specifically localized to the light-sensing organelle of the photoreceptor cell, the outer segment. Within the outer segment, peripherin is found at the edges of photoreceptor discs, where it plays a critical role in disc morphogenesis and maintenance. Peripherin loss or mutations are often associated with severe forms of visual impairments. Like all other resident outer segment proteins, peripherin is synthesized in the photoreceptor cell body and subsequently transported to the outer segment. In an effort to further examine peripherin's delivery to outer segments, we undertook a careful examination of its targeting sequence. Using a fluorescently labeled reporter expressed in the rods of transgenic tadpoles, we narrowed peripherin's targeting sequence to ten amino acids within its C-terminal tail. This small stretch of amino acid residues is both necessary and sufficient for outer segment targeting. We also conducted alanine scanning of all residues within this sequence and found that only a single residue, valine at position 332, is essential for outer segment targeting. This valine is conserved in all species and its mutation is sufficient to completely abrogate the targeting of full-length peripherin in mouse rods.
Peripherins Membrane Glycoproteins - metabolism Animals, Genetically Modified Membrane Glycoproteins - chemistry Structure-Activity Relationship Nerve Tissue Proteins - genetics Membrane Glycoproteins - genetics Anura Nerve Tissue Proteins - metabolism Nerve Tissue Proteins - chemistry Animals Larva Valine Photoreceptor Cells - metabolism Intermediate Filament Proteins - genetics Mice Intermediate Filament Proteins - metabolism Intermediate Filament Proteins - chemistry

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