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Vol. 15, Issue 4, 2027-2037, April 2004

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The C Terminus of Peripherin/rds Participates in Rod Outer Segment Targeting and Alignment of Disk Incisures

Beatrice M. Tam ^* , Orson L. Moritz ^*, and David S. Papermaster

Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06030

Submitted September 9, 2003; Revised December 31, 2003; Accepted December 31, 2003
Monitoring Editor: Keith Mostov

Protein targeting is essential for domain specialization in polarized cells. In photoreceptors, three distinct membrane domains exist in the outer segment: plasma membrane, disk lamella, and disk rim. Peripherin/retinal degeneration slow (rds) and rom-1 are photoreceptor-specific members of the transmembrane 4 superfamily of transmembrane proteins, which participate in disk morphogenesis and localize to rod outer segment (ROS) disk rims. We examined the role of their C termini in targeting by generating transgenic Xenopus laevis expressing green fluorescent protein (GFP) fusion proteins. A GFP fusion containing residues 317-336 of peripherin/rds localized uniformly to disk membranes. A longer fusion (residues 307-346) also localized to the ROS but exhibited higher affinity for disk rims than disk lamella. In contrast, the rom-1 C terminus did not promote ROS localization. The GFP-peripherin/rds fusion proteins did not immunoprecipitate with peripherin/rds or rom-1, suggesting this region does not form intermolecular interactions and is not involved in subunit assembly. Presence of GFP-peripherin/rds fusions correlated with disrupted incisures, disordered ROS tips, and membrane whorls. These abnormalities may reflect competition of the fusion proteins for other proteins that interact with peripherin/rds. This work describes novel roles for the C terminus of peripherin/rds in targeting and maintaining ROS structure and its potential involvement in inherited retinal degenerations.

Abbreviations used: GARP, glutamic acid rich protein; rds, retinal degeneration slow; RIS, rod inner segment; ROS, rod outer segment; TM4SF, transmembrane 4 superfamily.

^* Present address: Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, V6T 1Z3 Canada.

Corresponding author. E-mail address: btam{at}interchange.ubc.ca.

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