The cell biology of vision

Sung, Ching-Hwa; Chuang, Jen-Zen

doi:10.1083/jcb.201006020

Cited by 184 publications

(152 citation statements)

References 99 publications

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“…Although we can only speculate about the functional significance of such a phenomenon, one possibility is that it relates to phospholipid biosynthesis, as dihydroxyacetone phosphate serves as a precursor of glycerol-3-phosphate, the phospholipid backbone (72). Photoreceptors synthesize phospholipids at an unusually high rate because of the constant renewal of their outer segment membranes (73,74). The surface area of these membranes produced daily in a rat retina exceeds the surface area of the eyeball by over 50-fold (75).…”

Section: Averaging Protein Distribution Profiles Between Twomentioning

confidence: 99%

Proteomic Profiling of a Layered Tissue Reveals Unique Glycolytic Specializations of Photoreceptor Cells

Reidel

Thompson

Farsiu

et al. 2011

Molecular & Cellular Proteomics

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The retina is a highly ordered tissue whose outermost layers are formed by subcellular compartments of photoreceptors generating light-evoked electrical responses. We studied protein distributions among individual photoreceptor compartments by separating the entire photoreceptor layer of a flat-mounted frozen retina into a series of thin tangential cryosections and analyzing protein compositions of each section by label-free quantitative mass spectrometry. Based on 5038 confidently identified peptides assigned to 896 protein database entries, we generated a quantitative proteomic database (a "map") correlating the distribution profiles of identified proteins with the profiles of marker proteins representing individual compartments of photoreceptors and adjacent cells. We evaluated the applicability of several common peptide-toprotein quantification algorithms in the context of our database and found that the highest reliability was obtained by summing the intensities of all peptides representing a given protein, using at least the 5-6 most intense peptides when applicable. We used this proteome map to investigate the distribution of glycolytic enzymes, critical in fulfilling the extremely high metabolic demands of photoreceptor cells, and obtained two major findings. First, unlike the majority of neurons rich in hexokinase I, but similar to other highly metabolically active cells, photoreceptors express hexokinase II. Hexokinase II has a very high catalytic activity when associated with mitochondria, and indeed we found it colocalized with mitochondria in photoreceptors. Second, photoreceptors contain very little triosephosphate isomerase, an enzyme converting dihydroxyacetone phosphate into glyceraldehyde-3-phosphate. This may serve as a functional adaptation because dihydroxyacetone phosphate is a major precursor in phospholipid biosynthesis, a process particularly active in photoreceptors because of the constant renewal of their lightsensitive membrane disc stacks. Overall, our approach for proteomic profiling of very small tissue amounts at a resolution of a few microns, combining cryosectioning and liquid chromatography-tandem MS, can be applied for quantitative investigation of proteomes where spatial resolution is paramount.

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Section: Averaging Protein Distribution Profiles Between Twomentioning

confidence: 99%

Proteomic Profiling of a Layered Tissue Reveals Unique Glycolytic Specializations of Photoreceptor Cells

Reidel

Thompson

Farsiu

et al. 2011

Molecular & Cellular Proteomics

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“…For example, we know now how light can be transduced from a photon into a chemical signal that the brain can interpret (Sung and Chuang, 2010). We understand the specific cellular loss that contributes to Parkinson's disease (PD 1 ) (Przedborski, 2005).…”

Section: Introductionmentioning

confidence: 99%

Remote Control of Neuronal Signaling

2011

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“…Each stack includes hundreds of such disks, and is partially renewed each day by a balanced process of disk morphogenesis and shedding. Defects in OS structure and/or renewal profoundly impair photoreceptor function and viability and generate a variety of retinal diseases (Berger et al, 2010;Sung and Chuang, 2010).…”

Section: Introductionmentioning

confidence: 99%

Membrane curvature generation by a C-terminal amphipathic helix in peripherin-2/rds, a tetraspanin required for photoreceptor sensory cilium morphogenesis

Khattree

Ritter

Goldberg

2013

Journal of Cell Science

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SummaryVertebrate vision requires photon absorption by photoreceptor outer segments (OSs), structurally elaborate membranous organelles derived from non-motile sensory cilia. The structure and function of OSs depends on a precise stacking of hundreds of membranous disks. Each disk is fully (as in rods) or partially (as in cones) bounded by a rim, at which the membrane is distorted into an energetically unfavorable high-curvature bend; however, the mechanism(s) underlying disk rim structure is (are) not established. Here, we demonstrate that the intrinsically disordered cytoplasmic C-terminus of the photoreceptor tetraspanin peripherin-2/rds (P/rds) can directly generate membrane curvature. A P/rds C-terminal domain and a peptide mimetic of an amphipathic helix contained within it each generated curvature in liposomes with a composition similar to that of OS disks and in liposomes generated from native OS lipids. Association of the C-terminal domain with liposomes required conical phospholipids, and was promoted by membrane curvature and anionic surface charge, results suggesting that the P/rds C-terminal amphipathic helix can partition into the cytosolic membrane leaflet to generate curvature by a hydrophobic insertion (wedging) mechanism. This activity was evidenced in full-length P/rds by its induction of small-diameter tubulovesicular membrane foci in cultured cells. In sum, the findings suggest that curvature generation by the P/rds Cterminus contributes to the distinctive structure of OS disk rims, and provide insight into how inherited defects in P/rds can disrupt organelle structure to cause retinal disease. They also raise the possibility that tethered amphipathic helices can function for shaping cellular membranes more generally.

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The cell biology of vision

Cited by 184 publications

References 99 publications

Proteomic Profiling of a Layered Tissue Reveals Unique Glycolytic Specializations of Photoreceptor Cells

Proteomic Profiling of a Layered Tissue Reveals Unique Glycolytic Specializations of Photoreceptor Cells

Remote Control of Neuronal Signaling

Membrane curvature generation by a C-terminal amphipathic helix in peripherin-2/rds, a tetraspanin required for photoreceptor sensory cilium morphogenesis

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