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Tulp1 Is Involved in Specific Photoreceptor Protein Transport Pathways

  • Stephanie A. HagstromEmail author
  • Rao F. Watson
  • Gayle J. T. Pauer
  • Gregory H. Grossman
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 723)

Abstract

Tulp1 plays a critical role in protein transport from the photoreceptor inner segment (IS) to the outer segment (OS). To dissect which OS protein transport pathways are affected in the absence of Tulp1, we surveyed the localization of proteins destined for the OS in tulp1−/− mice. Immunohistochemistry was used to examine the localization of several classes of OS proteins as well as proteins involved in OS protein transport in young tulp1−/− mice prior to retinal degeneration. Comparisons were made to wild-type littermates. The absence of Tulp1 did not affect the transport of several phototransduction and OS structural proteins including phosphodiesterase, rhodopsin kinase, ROM-1, peripherin/RDS, and the cation channel. However, other phototransduction proteins such as rhodopsin, cone opsins, guanylate cyclase 1, and guanylate cyclase-activating proteins 1 and 2 were mislocalized to additional photoreceptor compartments. Two proteins that translocate in response to light stimulation were affected differently in tulp1−/− retinas; transducin translocated correctly whereas arrestin did not. In addition, chaperone proteins critical in the transport of rhodopsin-containing post-Golgi vesicles, Rab6, Rab8, and Rab11, were severely disrupted in tulp1−/− retinas. We conclude that Tulp1 is required for the correct transport of specific integral membrane proteins and their respective binding partners. Other classes of OS resident proteins do not appear to be affected. These differences support the hypothesis that Tulp1 plays a specific, critical role in photoreceptor OS protein transport pathways.

Keywords

Photoreceptor Retinal degeneration Tulp1 Mouse mutant Protein transport 

Notes

Acknowledgments

National Institute of Health Grants EY16072 and EY15638 (SAH), Foundation Fighting Blindness (SAH), Prevent Blindness Ohio (RFW), Fight For Sight (GHG), Research to Prevent Blindness (RPB) Center Grant, RPB Sybil B. Harrington Special Scholar Award (SAH), and Hope for Vision (SAH).

References

  1. Abbasi AH, Garzozi HJ, Ben-Yosef T (2008) A novel splice-site mutation of TULP1 underlies severe early-onset retinitis pigmentosa in a consanguineous Israeli Muslim Arab family. Mol Vis 14:675–682PubMedGoogle Scholar
  2. Banerjee P, Kleyn PW, Knowles JA et al (1998) TULP1 mutation in two extended Dominican kindreds with autosomal recessive retinitis pigmentosa. Nat Genet 18:177–179PubMedCrossRefGoogle Scholar
  3. Baehr W, Karan S, Maeda T et al (2007) The function of guanylate cyclase 1 and guanylate cyclase 2 in rod and cone photoreceptors. J Biol Chem 282:8837–8847PubMedCrossRefGoogle Scholar
  4. Berson EL (1993) Retinitis pigmentosa. The Friedenwald Lecture. Inves Ophthalmol Vis Sci 34:1659–1676Google Scholar
  5. Boughman JA, Conneally PM, Nance WE (1980) Population genetic studies of retinitis pigmentosa. Am J Hum Genet 32:223–235PubMedGoogle Scholar
  6. Bunker CH, Berson EL, Bromley WC et al (1984) Prevalence of retinitis pigmentosa in Maine. Am J Ophthalmol 97:357–365PubMedGoogle Scholar
  7. Calvert PD, Strissel KJ, Schiesser WE et al (2006) Light-driven translocation of signaling proteins in vertebrate photoreceptors. Trends Cell Biol 16:560–568PubMedCrossRefGoogle Scholar
  8. Deretic D (2006) A role for rhodopsin in a signal transduction cascade that regulates membrane trafficking and photoreceptor polarity. Vision Res 46:4427–4433PubMedCrossRefGoogle Scholar
  9. Grossman GH, Pauer GJ, Narendra U et al (2009) Early synaptic defects in tulp1−/− mice. Invest Ophthalmol Vis Sci 50:3074–3083PubMedCrossRefGoogle Scholar
  10. Grossman GH, Watson RF, Pauer GJT et al (2011) Tulp1-dependent Outer Segment Protein Transport Pathways in Photoreceptor Cells. Exp Eye Res Aug. 16 (Epub ahead of print)Google Scholar
  11. Gu S, Lennon A, Li Y et al (1998) Tubby-like protein-1 mutations in autosomal recessive retinitis pigmentosa. Lancet 351:1103–1104PubMedCrossRefGoogle Scholar
  12. Hagstrom SA, North MA, Nishina PL et al (1998) Recessive mutations in the gene encoding the tubby-like protein TULP1 in patients with retinitis pigmentosa. Nat Genet 18:174–176PubMedCrossRefGoogle Scholar
  13. Hagstrom SA, Duyao M, North MA et al (1999) Retinal degeneration in tulp1−/− mice: vesicular accumulation in the interphotoreceptor matrix. Invest Ophthalmol Vis Sci 40:2795–2802PubMedGoogle Scholar
  14. Hagstrom SA, Adamian M, Scimeca M et al (2001) A role for the Tubby-like protein 1 in rhodopsin transport. Invest Ophthalmol Vis Sci 42:1955–1962PubMedGoogle Scholar
  15. He W, Ikeda S, Bronson RT et al (2000) GFP-tagged expression and immunohistochemical studies to determine the subcellular localization of the tubby gene family members. Brain Res Mol Brain Res 81:109–117PubMedCrossRefGoogle Scholar
  16. Ikeda S, He W, Ikeda A et al (1999) Cell-specific expression of tubby gene family members (tub, Tulp1, 2, and 3) in the retina. Invest Ophthalmol Vis Sci 40:2706–2712PubMedGoogle Scholar
  17. Ikeda S, Shiva N, Ikeda A et al (2000) Retinal degeneration but not obesity is observed in null mutants of the tubby-like protein 1 gene. Hum Mol Genet 9:155–163PubMedCrossRefGoogle Scholar
  18. Karan S, Zhang H, Li S et al (2008) A model for transport of membrane-associated phototransduction polypeptides in rod and cone photoreceptor inner segments. Vision Res 48:442–452PubMedCrossRefGoogle Scholar
  19. Kleyn PW, Fan W, Kovats SG et al (1996) Identification and characterization of the mouse obesity gene tubby: a member of a novel gene family. Cell 85:281–290PubMedCrossRefGoogle Scholar
  20. Mataftsi A, Schorderet DF, Chachoua L et al (2007) Novel TULP1 mutation causing leber congenital amaurosis or early onset retinal degeneration. Invest Ophthalmol Vis Sci 48:5160–5167PubMedCrossRefGoogle Scholar
  21. Nishina PM, North MA, Ikeda A et al (1998) Molecular characterization of a novel tubby gene family member, TULP3, in mouse and humans. Genomics 54:215–220PubMedCrossRefGoogle Scholar
  22. North MA, Naggert JK, Yan Y et al (1997) Molecular characterization of TUB, TULP1, and TULP2, members of the novel tubby gene family and their possible relation to ocular diseases. Proc Natl Acad Sci USA 94:3128–3133PubMedCrossRefGoogle Scholar
  23. Norton AW, Hosier S, Terew JM et al (2005) Evaluation of the 17-kDa prenyl-binding protein as a regulatory protein for phototransduction in retinal photoreceptors. J Biol Chem 280:1248–1256PubMedCrossRefGoogle Scholar
  24. Paloma E, Hjelmqvist L, Bayes M et al (2000) Novel mutations in the TULP1 gene causing autosomal recessive retinitis pigmentosa. Invest Ophthalmol Vis Sci 41:656–659PubMedGoogle Scholar
  25. Sahly I, Gogat K, Kobetz A et al (1998) Prominent neuronal-specific tub gene expression in cellular targets of tubby mice mutation. Hum Mol Genet 7:1437–1447PubMedCrossRefGoogle Scholar
  26. Slepak VZ, Hurley JB (2008). Mechanism of light-induced translocation of arrestin and transducin in photoreceptors: interaction-restricted diffusion. IUBMB Life 60:2–9PubMedCrossRefGoogle Scholar
  27. Xi Q, Pauer GJ, Marmorstein AD et al (2005) Tubby-like protein 1 (TULP1) interacts with F-actin in photoreceptor cells. Invest Ophthalmol Vis Sci 46:4754–4761PubMedCrossRefGoogle Scholar
  28. Xi Q, Pauer GJ, Ball SL et al (2007) Interaction between the photoreceptor-specific tubby-like protein 1 and the neuronal-specific GTPase dynamin-1. Invest Ophthalmol Vis Sci 48:2837–2844PubMedCrossRefGoogle Scholar
  29. Yang RB, Robinson SW, Xiong WH et al (1999) Disruption of a retinal guanylyl cyclase gene leads to cone-specific dystrophy and paradoxical rod behavior. J Neurosci 19:5889–5897PubMedGoogle Scholar
  30. Zhang H, Li S, Dhoan T et al (2007) Deletion of PrBP/delta impedes transport of GRK1 and PDE6 catalytic subunits to photoreceptor outer segments. Proc Natl Acad Sci USA 104:8857–8862PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Stephanie A. Hagstrom
    • 1
    • 2
    Email author
  • Rao F. Watson
    • 1
  • Gayle J. T. Pauer
    • 1
  • Gregory H. Grossman
    • 1
  1. 1.Department of Ophthalmic ResearchCole Eye Institute, Cleveland ClinicClevelandUSA
  2. 2.Department of OphthalmologyCleveland Clinic Lerner College of Medicine of Case Western Reserve UniversityClevelandUSA

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