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PMID: 17693260 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

SARA-regulated vesicular targeting underlies formation of the light-sensing organelle in mammalian rods.

Cell ·Vol. 130 ·No. 3 ·2007-08-10 ·Pages 535-47

Chuang JZ, Zhao Y, Sung CH

Abstract

The light-sensing organelle of the vertebrate rod photoreceptor, the outer segment (OS), is a modified cilium containing approximately 1,000 stacked disc membranes that are densely packed with visual pigment rhodopsin. The mammalian OS is renewed every ten days; new discs are assembled at the base of the OS by a poorly understood mechanism. Our results suggest that discs are formed and matured in a process that involves specific phospholipid-directed vesicular membrane targeting. Rhodopsin-laden vesicles in the OS axonemal cytoplasm fuse with nascent discs that are highly specialized with abundant phosphatidylinositol 3-phosphate (PI3P). This membrane coupling is regulated by the FYVE domain-containing protein, SARA, through its direct interaction with PI3P, rhodopsin, and SNARE protein syntaxin 3. Our model, in contrast to the previously proposed evagination model, suggests that the vesicular delivery of rhodopsin in the OS concentrates rhodopsin into discs, and this process directly participates in disc biogenesis.

MeSH Terms
Animals Animals, Genetically Modified Animals, Newborn Cell Differentiation/physiology Cell Line Cytoplasmic Vesicles/metabolism Humans Intracellular Signaling Peptides and Proteins/antagonists & inhibitors,genetics,physiology Light Mice Organelles/metabolism Peptide Fragments/metabolism Rats Rhodopsin/metabolism Rod Cell Outer Segment/cytology Serine Endopeptidases/genetics,physiology
Chemicals
Intracellular Signaling Peptides and Proteins Peptide Fragments Rhodopsin ZFYVE16 protein, human Serine Endopeptidases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Chuang Jen-Zen
Margaret M. Dyson Vision Research Institute, Department of Ophthalmology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA. izchuang@med.cornell.edu
Zhao Yu
Sung Ching-Hwa
References (46)
46 references, click to expand
  1. Rhodopsin C terminus, the site of mutations causing retinal disease, regulates trafficking by binding to ADP-ribosylation factor 4 (ARF4).
    Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3301-6 PMID: 15728366
  2. The Rab5 effector EEA1 interacts directly with syntaxin-6.
    J Biol Chem. 1999 Oct 8;274(41):28857-60 PMID: 10506127
  3. Apical targeting of syntaxin 3 is essential for epithelial cell polarity.
    J Cell Biol. 2006 Jun 19;173(6):937-48 PMID: 16785322
  4. Retinal degeneration in tulp1-/- mice: vesicular accumulation in the interphotoreceptor matrix.
    Invest Ophthalmol Vis Sci. 1999 Nov;40(12):2795-802 PMID: 10549638
  5. Differential roles of syntaxin 7 and syntaxin 8 in endosomal trafficking.
    Mol Biol Cell. 1999 Nov;10(11):3891-908 PMID: 10564279
  6. FYVE-finger proteins--effectors of an inositol lipid.
    J Cell Sci. 1999 Dec;112 ( Pt 23):4175-83 PMID: 10564636
  7. A retinitis pigmentosa GTPase regulator (RPGR)-deficient mouse model for X-linked retinitis pigmentosa (RP3).
    Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3649-54 PMID: 10725384
  8. Localization of phosphatidylinositol 3-phosphate in yeast and mammalian cells.
    EMBO J. 2000 Sep 1;19(17):4577-88 PMID: 10970851
  9. Distinct oligomeric states of SMAD proteins in the transforming growth factor-beta pathway.
    J Biol Chem. 2000 Dec 29;275(52):40710-7 PMID: 11018029
  10. Endofin, an endosomal FYVE domain protein.
    J Biol Chem. 2001 Nov 9;276(45):42445-54 PMID: 11546807
  11. The FYVE domain in Smad anchor for receptor activation (SARA) is sufficient for localization of SARA in early endosomes and regulates TGF-beta/Smad signalling.
    Genes Cells. 2002 Mar;7(3):321-31 PMID: 11918675
  12. SARA, a FYVE domain protein, affects Rab5-mediated endocytosis.
    J Cell Sci. 2002 Dec 15;115(Pt 24):4755-63 PMID: 12432064
  13. Arrestin migrates in photoreceptors in response to light: a study of arrestin localization using an arrestin-GFP fusion protein in transgenic frogs.
    Exp Eye Res. 2003 May;76(5):553-63 PMID: 12697419
  14. Light-dependent translocation of arrestin in the absence of rhodopsin phosphorylation and transducin signaling.
    J Neurosci. 2003 Apr 15;23(8):3124-9 PMID: 12716919
  15. The phosphoinositide (PI) 3-kinase family.
    J Cell Sci. 2003 Aug 1;116(Pt 15):3037-40 PMID: 12829733
  16. Human VPS34 and p150 are Rab7 interacting partners.
    Traffic. 2003 Nov;4(11):754-71 PMID: 14617358
  17. Electroporation and RNA interference in the rodent retina in vivo and in vitro.
    Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):16-22 PMID: 14603031
  18. Structural and functional impairment of endocytic pathways by retinitis pigmentosa mutant rhodopsin-arrestin complexes.
    J Clin Invest. 2004 Jul;114(1):131-40 PMID: 15232620
  19. The renewal of photoreceptor cell outer segments.
    J Cell Biol. 1967 Apr;33(1):61-72 PMID: 6033942
  20. Rods and cones in the mouse retina. I. Structural analysis using light and electron microscopy.
    J Comp Neurol. 1979 Nov 15;188(2):245-62 PMID: 500858
  21. Disc morphogenesis in vertebrate photoreceptors.
    J Comp Neurol. 1980 Apr 1;190(3):501-8 PMID: 6771304
  22. Retinal degeneration in the pcd cerebellar mutant mouse. II. Electron microscopic analysis.
    J Comp Neurol. 1982 Dec 10;212(3):231-46 PMID: 7153375
  23. Light and temperature modulated staining of the rod outer segment distal tips with Lucifer yellow.
    Invest Ophthalmol Vis Sci. 1985 May;26(5):628-35 PMID: 2581915
  24. Disruption of microfilament organization and deregulation of disk membrane morphogenesis by cytochalasin D in rod and cone photoreceptors.
    J Comp Neurol. 1988 Jun 8;272(2):161-76 PMID: 3397406
  25. Light-dependent subcellular movement of photoreceptor proteins.
    J Neurosci Res. 1988;20(2):263-70 PMID: 3172281
  26. The cGMP-gated channel of bovine rod photoreceptors is localized exclusively in the plasma membrane.
    J Biol Chem. 1989 Apr 25;264(12):6996-9 PMID: 2468664
  27. Evidence for the transport of opsin in the connecting cilium and basal rod outer segment in rat retina: rapid-freeze, deep-etch and horseradish peroxidase labelling studies.
    J Neurocytol. 1992 Jun;21(6):449-57 PMID: 1383431
  28. Morphogenesis of the photoreceptor outer segment during postnatal development in the mouse (BALB/c) retina.
    Cell Tissue Res. 1992 Jul;269(1):39-48 PMID: 1423483
  29. SNAP receptors implicated in vesicle targeting and fusion.
    Nature. 1993 Mar 25;362(6418):318-24 PMID: 8455717
  30. A rhodopsin gene mutation responsible for autosomal dominant retinitis pigmentosa results in a protein that is defective in localization to the photoreceptor outer segment.
    J Neurosci. 1994 Oct;14(10):5818-33 PMID: 7523628
  31. Constitutive activation of phototransduction by K296E opsin is not a cause of photoreceptor degeneration.
    Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3551-5 PMID: 7724596
  32. Transgenic mice carrying the dominant rhodopsin mutation P347S: evidence for defective vectorial transport of rhodopsin to the outer segments.
    Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):14176-81 PMID: 8943080
  33. Differential localization of syntaxin isoforms in polarized Madin-Darby canine kidney cells.
    Mol Biol Cell. 1996 Dec;7(12):2007-18 PMID: 8970161
  34. Distinct cellular locations of the syntaxin family of proteins in rat pancreatic acinar cells.
    Mol Biol Cell. 1996 Dec;7(12):2019-27 PMID: 8970162
  35. Retinopathy induced in mice by targeted disruption of the rhodopsin gene.
    Nat Genet. 1997 Feb;15(2):216-9 PMID: 9020854
  36. Association of syntaxin 3 and vesicle-associated membrane protein (VAMP) with H+/K(+)-ATPase-containing tubulovesicles in gastric parietal cells.
    Mol Biol Cell. 1997 Mar;8(3):399-407 PMID: 9188093
  37. ER-to-Golgi transport visualized in living cells.
    Nature. 1997 Sep 4;389(6646):81-5 PMID: 9288971
  38. Syntaxin 7, a novel syntaxin member associated with the early endosomal compartment.
    J Biol Chem. 1998 Jan 2;273(1):375-80 PMID: 9417091
  39. Rhodopsin transgenic pigs as a model for human retinitis pigmentosa.
    Invest Ophthalmol Vis Sci. 1998 Apr;39(5):808-19 PMID: 9538889
  40. FYVE fingers bind PtdIns(3)P.
    Nature. 1998 Jul 30;394(6692):432-3 PMID: 9697764
  41. SARA, a FYVE domain protein that recruits Smad2 to the TGFbeta receptor.
    Cell. 1998 Dec 11;95(6):779-91 PMID: 9865696
  42. Morphological, physiological, and biochemical changes in rhodopsin knockout mice.
    Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):736-41 PMID: 9892703
  43. The Rab5 effector EEA1 is a core component of endosome docking.
    Nature. 1999 Feb 18;397(6720):621-5 PMID: 10050856
  44. Rhodopsin's carboxy-terminal cytoplasmic tail acts as a membrane receptor for cytoplasmic dynein by binding to the dynein light chain Tctex-1.
    Cell. 1999 Jun 25;97(7):877-87 PMID: 10399916
  45. Oligomeric complexes link Rab5 effectors with NSF and drive membrane fusion via interactions between EEA1 and syntaxin 13.
    Cell. 1999 Aug 6;98(3):377-86 PMID: 10458612
  46. Light-dependent redistribution of arrestin in vertebrate rods is an energy-independent process governed by protein-protein interactions.
    Neuron. 2005 May 19;46(4):555-67 PMID: 15944125
Article Info
Journal
Cell
Abbr.
Cell
ISSN
0092-8674
DOI
10.1016/j.cell.2007.06.030
Email
izchuang@med.cornell.edu
Published
2007-08-10
Pages
535-47
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC3857750
Subset
IM
Grants
NEI NIH HHS · R01 EY011307 · United States
NEI NIH HHS · R01 EY016805 · United States
NEI NIH HHS · EY11307 · United States
External Links
PubMed source DOI: 10.1016/j.cell.2007.06.030 PMC Full Text View journal details
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