Photoreceptor renewal: A role for peripherin/rds

Boesze‐Battaglia, Kathleen; Goldberg, Andrew F.X.

doi:10.1016/s0074-7696(02)17015-x

Cited by 52 publications

(48 citation statements)

References 183 publications

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“…The post-Golgi vesicles that transport rhodopsin have a unique phospholipid composition, containing phosphatidylcholine and phosphatidylethanolamine with docosahexaenoyl (DHA) acyl chains [64]. Modification of phospholipid biosynthesis affected fusion and budding of the transport membranes differently [65] Furthermore, the organization of cholesterol within the disk membranes may also be determined prior to the formation of a new disk [66].…”

Section: Cholesterol Distribution Among Ros Membranesmentioning

confidence: 99%

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The role of cholesterol in rod outer segment membranes

Albert

Boesze‐Battaglia

2005

Progress in Lipid Research

112

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The photoreceptor rod outer segment (ROS) provides a unique system in which to investigate the role of cholesterol, an essential membrane constituent of most animal cells. The ROS is responsible for the initial events of vision at low light levels. It consists of a stack of disk membranes surrounded by the plasma membrane. Light capture occurs in the outer segment disk membranes that contain the photopigment, rhodopsin. These membranes originate from evaginations of the plasma membrane at the base of the outer segment. The new disks separate from the plasma membrane and progressively move up the length of the ROS over the course of several days. Thus the role of cholesterol can be evlauated in two distinct membranes. Furthermore, because the disk membranes vary in age it can also be investigated in a membrane as a function of the membrane age. The plasma membrane is enriched in cholesterol and in saturated fatty acids species relative to the disk membrane. The newly formed disk membranes have 6-fold more cholesterol than disks at the apical tip of the ROS. The partitioning of cholesterol out of disk membranes as they age and are apically displaced is consistent with the high PE content of disk membranes relative to the plasma membrane. The cholesterol composition of membranes has profound consequences on the major protein, rhodopsin. Biophysical studies in both model membranes and in native membranes have demonstrated that cholesterol can modulate the activity of rhodopsin by altering the membrane hydrocarbon environment. These studies suggest that mature disk membranes initiate the visual signal cascade more effectively than the newly synthesized, high cholesterol basal disks. Although rhodopsin is also the major protein of the plasma membrane, the high membrane cholesterol content inhibits rhodopsin participation in the visual transduction cascade. In addition to its effect on the hydrocarbon region, cholesterol may interact directly with rhodopsin. While high cholesterol inhibits rhodopsin activation, it also stabilizes the protein to denaturation. Therefore the disk membrane must perform a balancing act providing sufficient cholestrol to confer stability but without making the membrane too restrictive to receptor activation. Within a given disk membrane, it is likely that cholesterol exhibits an asymmetric distribution between the inner and outer bilayer leaflets. Furthremore, there is some evidence of cholesterol microdomains in the disk membranes. The availability of the disk protein, rom-1 may be sensitive to membrane cholesterol. The effects exerted by cholesterol on rhodopsin function have far-reaching implications for the study of G-protein coupled receptors as a whole. These studies show that the function of a membrane receptor can be modulated by modification of HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript the lipid bilayer, particularly cholesterol. This provides a powerful means of fine-tuning the activity of a membrane protein without resorting ...

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Section: Cholesterol Distribution Among Ros Membranesmentioning

confidence: 99%

“…These studies have provided in vitro evidence that the product of the RDS gene, peripherin/rds (a.k.a. peripherin-2) functions as a photoreceptor specific membrane fusion protein [125,126] and for review [66].…”

Section: Organization Of Cholesterol In Disk Membranesmentioning

confidence: 99%

The role of cholesterol in rod outer segment membranes

Albert

Boesze‐Battaglia

2005

Progress in Lipid Research

112

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“…Periph-erin/rds participates in the maintenance of normal ROS disk membrane structure and in disk morphogenesis and shedding (Ref. 15 and references therein) and acts as a photoreceptorspecific fusion protein (16,17).…”

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confidence: 99%

Association of a Photoreceptor-specific Tetraspanin Protein, ROM-1, with Triton X-100-resistant Membrane Rafts from Rod Outer Segment Disk Membranes

Boesze‐Battaglia¹,

Dispoto²,

Kahoe³

2002

Journal of Biological Chemistry

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This study reports the isolation and characterization of a Triton X-100-resistant membrane fraction from homogenates of rod outer segment (ROS) disk membranes purified free of the surrounding plasma membrane. A portion of the ROS disk membrane was found to be resistant to Triton X-100 extraction at 4°C. This detergent-resistant fraction was isolated as a low buoyant density band on sucrose density gradients and exhibited an increase in light scattering detected at 600 nm. Biochemical analysis of the Triton X-100-resistant fraction showed it to be enriched in cholesterol and sphingomyelin relative to phospholipid and in phospholipid relative to protein compared with the soluble fraction. The Triton X-100-resistant membranes described herein did not arise simply from partial solubilization of the ROS disk membranes because detergent-treated low buoyant density fractions isolated from homogenates with octyl glucopyranoside had cholesterol and sphingomyelin content indistinguishable from that of solubilized ROS disk homogenates. Analysis of proteins associated with the Triton X-100-resistant fraction showed it to be enriched in the rim-specific protein ROM-1 and caveolin; surprisingly, the fusion protein peripherin/rds (where rds is retinal degeneration slow), also localized to the disk rim, was entirely absent from the membrane raft domain. The lipid profiles of the Triton X-100-resistant membranes were virtually identical in preparations homogenized in either the light or dark. Slightly more ROM-1 was recovered from samples prepared in the light (23%) than from samples prepared in the dark (13%), but peripherin/rds could not be detected in either preparation. When the Triton X-100-resistant membranes were treated with methyl-␤-cyclodextran to deplete membrane cholesterol, the resultant membranes contained slightly lower levels of ROM-1, specifically in the dimeric form. Cholesterol depletion also resulted in the collapse of the large caveolin complex to monomeric caveolae. The results presented herein characterize a pool of ROM-1, a photoreceptor tetraspanin protein, that may play a regulatory role in peripherin/rds-dependent fusion.Photoreceptor rod cells are responsible for vision under dim light. These unique post-mitotic cells are made up of a rod inner segment and a rod outer segment (ROS) 1 region. The ROS contains a stack of closed membranous sacs, referred to as disks, that contain the photoreceptor rhodopsin and that provide the requisite lipid environment for the initial events of phototransduction. There is a continual turnover of disk membranes and the proteins contained therein. Through coordinated processes of disk renewal at the base of the outer segment and disk shedding at the apical tip, the outer segment region is maintained at a constant length, and the physiologic function of light transduction is maintained (1). Interestingly, although the distribution of the major proteins within disks remains constant during the basal-to-apical transit of disks, a process that requires 10 days in the verteb...

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“…Both of these processes requires tightly regulated membrane fusion events, in the delivery of new membraneous material from the IS (Deretic and Papermaster 1991;Deretic and Papermaster 1993;Deretic and Papermaster 1995;Chuang, Vega et al 2004), for disk closure during morphogenesis (Steinberg, Fisher et al 1980;BoeszeBattaglia and Goldberg 2002) and in disk packet formation and shedding (Boesze-Battaglia and Goldberg 2002;Chen, Yunhai et al 2002). Previous studies in our laboratory have suggested that disks at the apical tip of the OS fuse spontaneously to delineate a packet of disks (Boesze-Battaglia 1997) and that the tetraspanin protein, peripherin/rds (P/rds a.k.a.…”

Section: Introductionmentioning

confidence: 99%

ROM-1 potentiates photoreceptor specific membrane fusion processes

Boesze‐Battaglia

Stefano

Fitzgerald

et al. 2007

Experimental Eye Research

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Photoreceptor outer segment (OS) renewal requires a series of tightly regulated membrane fusion events which are mediated by a fusion complex containing protein and lipid components. The best characterized of these components, is a unique photoreceptor specific tetraspanin, peripherin/rds (P/ rds, a.k.a., peripherin-2, Rds and Prph). In these studies we investigated the role of peripherin's nonglycosylated homolog, ROM-1, in OS fusion using a COS cell heterologous expression system and a well characterized cell free fusion assay system. Membranes isolated from COS-7 cells transfected with either FLAG-tagged P/rds or HA-tagged ROM-1 or both proteins were assayed for their ability to merge with fluorescently labeled OS plasma membrane (PM). Such membrane merger is one measure of membrane fusogenicity. The highest percent fusion was observed when the proteins were co-expressed. Furthermore detailed analysis of the fusion kinetics between fluorescently labeled PM and proteo-liposomes containing either, pure P/rds, pure ROM-1 or the ROM-1-P/rds complex clearly demonstrated that optimal fusion requires an ROM-P/rds1 complex. Proteo-liposomes composed of ROM-1 alone were not fusogenic. Peptide competition studies suggest that optimization of fusion may be due to the formation of a fusion competent peripherin/rds C-terminus in the presence of ROM-1. These studies provide further support for the hypothesis that a P/rds dependent membrane fusion complex is involved in photoreceptor renewal processes.

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Photoreceptor renewal: A role for peripherin/rds

Cited by 52 publications

References 183 publications

The role of cholesterol in rod outer segment membranes

The role of cholesterol in rod outer segment membranes

Association of a Photoreceptor-specific Tetraspanin Protein, ROM-1, with Triton X-100-resistant Membrane Rafts from Rod Outer Segment Disk Membranes

ROM-1 potentiates photoreceptor specific membrane fusion processes

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