The photoreceptors and pigment epithelium of the larval<i>Xenopus</i>retina: morphogenesis and outer segment renewal

Kinney, Marion S.; Fisher, Steven K.

doi:10.1098/rspb.1978.0037

Cited by 57 publications

(12 citation statements)

References 45 publications

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“…How has electron microscopy of the base of the OS convincingly shown plasma membrane evaginations (4,7,8) in some studies and vesicles apparently enclosed by plasma membrane in others (5,12)? We have shown that the method of specimen preparation is key to preservation of the IS:OS interface.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, the fusion model proposes that discs originate from rhodopsincontaining vesicles, which undergo homotypic fusion to form new discs (5, 6). Conventional electron microscopic (EM) analyses of chemically fixed specimens have clearly shown discs open to the extracellular space at the base of the OS, supporting the evagination model (4,7,8). Furthermore, studies in amphibians have demonstrated that membrane impermeant dyes can stain discs at the base of the rod OS, indicating they are not enclosed by plasma membrane (9, 10).…”

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confidence: 99%

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Rod disc renewal occurs by evagination of the ciliary plasma membrane that makes cadherin-based contacts with the inner segment

Burgoyne

Meschede

Burden

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

105

103

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The outer segments of vertebrate rod photoreceptors are renewed every 10 d. Outer segment components are transported from the site of synthesis in the inner segment through the connecting cilium, followed by assembly of the highly ordered discs. Two models of assembly of discrete discs involving either successive fusion events between intracellular rhodopsin-bearing vesicles or the evagination of the plasma membrane followed by fusion of adjacent evaginations have been proposed. Here we use immuno-electron microscopy and electron tomography to show that rhodopsin is transported from the inner to the outer segment via the ciliary plasma membrane, subsequently forming successive evaginations that "zipper" up proximally, but at their leading edges are free to make junctions containing the protocadherin, PCDH21, with the inner segment plasma membrane. Given the physical dimensions of the evaginations, coupled with likely instability of the membrane cortex at the distal end of the connecting cilium, we propose that the evagination occurs via a process akin to blebbing and is not driven by actin polymerization. Disassembly of these junctions is accompanied by fusion of the leading edges of successive evaginations to form discrete discs. This fusion is topologically different to that mediated by the membrane fusion proteins, SNAREs, as initial fusion is between exoplasmic leaflets, and is accompanied by gain of the tetraspanin rim protein, peripherin.rod photoreceptors | disc renewal | rhodopsin | protocadherin R od photoreceptors are specialized neurons of the vertebrate retina responsible for vision in dim light. The cylindrical outer segment (OS) contains ∼1,000 stacked discontinuous membranous discs packed with the light-sensitive pigment rhodopsin. This contrasts with the cone OS, which consists of a series of evaginations of the plasma membrane that remain exposed to the extracellular space (1). OS constituents are synthesized in the inner segment (IS) and then transported to the OS via a nonmotile cilium (connecting cilium) that resembles the transition zone of the primary cilium. Because of the high metabolic demand of phototransduction, OS discs undergo daily renewal, whereby the tip (distal end) is shed and phagocytosed by the retinal pigment epithelium while new discs are formed at the base (proximal end) of the OS (2, 3). How these discs are generated and rhodopsin incorporated remains controversial. The evagination model proposes that the ciliary plasma membrane evaginates to form discs that are initially exposed to the extracellular space and then pinch off to form fully closed discs (4). In contrast, the fusion model proposes that discs originate from rhodopsincontaining vesicles, which undergo homotypic fusion to form new discs (5, 6). Conventional electron microscopic (EM) analyses of chemically fixed specimens have clearly shown discs open to the extracellular space at the base of the OS, supporting the evagination model (4,7,8). Furthermore, studies in amphibians have demonstrated that membrane imper...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Rod disc renewal occurs by evagination of the ciliary plasma membrane that makes cadherin-based contacts with the inner segment

Burgoyne

Meschede

Burden

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

105

103

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“…The only OS sites that have been identified as growing fronts are the small number of incomplete basal lamellae, which expand by growing away from the cilium and are therefore best considered to be evaginations (Kinney and Fisher, 1978b;Anderson et al, 1978) rather than invaginations, as they were originally described (Sj6strand, 1961). Because such partially formed membrane outfoldings are consistently found at the extreme base of rod and cone OS and have not been described at other OS levels, I suggest they be termed"basal evaginations" (BE).…”

mentioning

confidence: 99%

“…In COS, as in ROS, newly synthesized membrane is apparently added by sclerad flow of the ciliary membrane at the OS base (Kinney and Fisher, 1978b;Holtzman and Mercurio, 1980;Papermaster and Schneider, 1982) and packets of membranes are discarded from the OS tip, but the intervening processes by which membrane is incorporated into the COS and travels from the base to the tip are not well understood. It is generally assumed (Young, 1976;Bok, 1985;Anderson et al, 1986;Roof, 1986) that COS exhibit no localLzation of autoradiographic labeling because molecules quickly diffuse throughout their fluid and topologically continuous membrane system, but the rate of longitudinal diffusion within COS membranes is not certain (of.…”

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confidence: 99%

Cone outer segment morphogenesis: taper change and distal invaginations.

Eckmiller

1987

The Journal of Cell Biology

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Abstract. Because cone outer segments (COS) are now known to be continually renewed, I reexamined COS morphogenesis in retinas of Xenopus tadpoles (prepared by standard histologic techniques and viewed by light and electron microscopy) to clarify how COS incorporate new membrane. I observed that developing COS underwent an unexpected shape change: they were always conical, but their taper (width divided by length) continually decreased. Ultrastructural examination revealed that many of the membrane foldings within distal COS were partial or incomplete, not extending across the full COS width but ending at variable distances from the ciliary side. Because these partial folds represented infoldings of the plasma membrane of an existing lamella, and they occurred at all COS levels except the base, I have termed them distal invaginations (DI). The completion of each DI increased COS length by one lamella but caused no noticeable change in local COS width; thus the formation of many DI throughout the distal COS presumably resulted in the observed decrease in overall COS taper. Based on these findings, I suggest that DI indicate growing membrane fronts and may represent sites where newly synthesized membrane is incorporated into COS. Because DI occur in developing and adult COS of various vertebrate species, I propose that DI formation plays an important role in the generation of COS taper during development and the remodeling of COS taper in mature cones after tip shedding.THOtJGI-I it is now accepted that the light-sensitive outer segments (OS) ~ of both vertebrate rods and cones are regularly renewed (Anderson et al., 1978;Young, 1978;Bok, 1985;Roof, 1986), numerous aspects of cone outer segment (COS) renewal remain problematical. I have reexamined the morphogenesis of COS to clarify how new membrane is incorporated into COS.Rod outer segment (ROS) membranes are renewed in a very orderly manner, as first revealed by autoradiography (Young, 1967): radioactive protein molecules become trapped in new membranous disks generated at the OS base, producing an autoradiographic band of label; the unchanged band is displaced sclerally as additional disks form below, and finally discarded from the OS tip and phagocytized by the pigment epithelium (Young and Bok, 1969). This pattern of membrane renewal is consistent with the ultrastructural morphology and cylindrical shape of mature ROS (Young, 1976;Steinberg et al., 1980;Bok, 1985). It is thus clear how new membrane is incorporated into ROS: each membrane entering via the connecting cilium becomes distributed into successive new membrane folds that evaginate from the cilium at the OS base, these evaginations expand to the full OS width and are displaced away from the base, then lose their 1. Abbreviations used in thispaper: BE, basal evagination; COS, cone outer segment; DI, distal invagination; LM, light microscopy; OS, outer segment; ROS, rod outer segment.connections and become isolated into separate disks surrounded by the plasma membrane.COS differ from ROS in structural...

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“…However, these results are also consistent with alternative explanations, e.g., comigration or fusion of radiolabeled RIS-derived membranes containing newly synthesized, nonglycosylated opsin with unlabeled, previously formed ROS membranes during the isolation procedures. In this regard, electron microscopic and immunocytochemical studies have revealed the presence of opsin-containing vesicles in the periciliary region of the RIS cytoplasm, proximal to the ROS (7,29,47,48). In contrast, biochemical and light microscopic autoradiographic evidence from the study using Rana retinas (12) demonstrated that TM-mediated inhibition of opsin glycosylation resulted in a lack of assembly of opsin into new ROS membranes.…”

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confidence: 99%

Membrane morphogenesis in retinal rod outer segments: inhibition by tunicamycin.

Fliesler¹,

Rayborn²,

Hollyfield³

1985

The Journal of Cell Biology

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Isolated Xenopus laevis retinas were incubated with 3H-labeled mannose or leucine in the presence or absence of tunicamycin (TM), a selective inhibitor of dolichyl phosphatedependent protein glycosylation. At a TM concentration of 20 /~g/ml, the incorporation of [3H]mannose and [3H]leucine into retinal macromolecules was inhibited by ~66 and 12-16%, respectively, relative to controls. Cellular uptake of the radiolabeled substrates was not inhibited at this TM concentration. Polyacrylamide gel electrophoresis revealed that TM had little effect on the incorporation of [3H]leucine into the proteins of whole retinas and that labeling of proteins (especially opsin) in isolated rod outer segment (ROS) membranes was negligible. The incorporation of [3H]mannose into proteins of whole retinas and ROS membranes was nearly abolished in the presence of TM. Autoradiograms of control retinas incubated with either [31-1]mannose or [3H]leucine exhibited a discrete concentration of silver grains over ROS basal disc membranes. In TM-treated retinas, the extracellular space between rod inner and outer segments was dilated and filled with numerous heterogeneously size vesicles, which were labeled with [3H]leucine but not with [3H]mannose. ROS disc membranes per se were not labeled in the TM-treated retinas. Quantitative light microscopic autoradiography of retinas pulse-labeled with [3H]leucine showed no differences in labeling of rod cellular compartments in the presence or absence of TM as a function of increasing chase time. These results demonstrate that TM can block retinal protein glycosylation and normal disc membrane assembly under conditions where synthesis and intracellular transport of rod cell proteins (e.g., opsin) are not inhibited.The rod photoreceptor in the vertebrate retina is a structurally and functionally polarized and segmented postmitotic cell. The rod outer segment (ROS) ~ is composed of a highly ordered stack of individual, flattened double-membrane saccules (the disc membranes) enveloped by the plasma membrane of the cell. The photosensitive nature of the ROS is due to the presence of rhodopsin, the rod visual pigment, in the disc membranes. The ROS is attached to the adjacent rod inner segment (RIS) by the connecting cilium, a narrow cytoplasmic bridge through which intracellular exchange and flow of cytoplasmic constituents takes place. The RIS, which contains the organelles of anabolic and catabolic metabolism, is compartmentalized into two regions: the ellipsoid and the myoid. The ellipsoid (proximal to the connecting cilium) is filled with Abbreviations used in this paper. ITV, intracellular transport vesicle; TCA, trichloroacetic acid; RIS, rod inner segment; ROS, rod outer segment. a dense cluster of mitochondria, whereas the myoid (distal to the nucleus) houses an extensive network of endoplasmic reticulum and the Golgi apparatus.The rod cell renews the ROS membranes at a prodigious rate in an ongoing process throughout its lifetime (47,64,65). For instance, in the African clawed toad Xeno...

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The photoreceptors and pigment epithelium of the larvalXenopusretina: morphogenesis and outer segment renewal

Cited by 57 publications

References 45 publications

Rod disc renewal occurs by evagination of the ciliary plasma membrane that makes cadherin-based contacts with the inner segment

Rod disc renewal occurs by evagination of the ciliary plasma membrane that makes cadherin-based contacts with the inner segment

Cone outer segment morphogenesis: taper change and distal invaginations.

Membrane morphogenesis in retinal rod outer segments: inhibition by tunicamycin.

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