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.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
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 14:675–682
Banerjee P, Kleyn PW, Knowles JA et al (1998) TULP1 mutation in two extended Dominican kindreds with autosomal recessive retinitis pigmentosa. Nat Genet 18:177–179
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 282:8837–8847
Berson EL (1993) Retinitis pigmentosa. The Friedenwald Lecture. Inves Ophthalmol Vis Sci 34:1659–1676
Boughman JA, Conneally PM, Nance WE (1980) Population genetic studies of retinitis pigmentosa. Am J Hum Genet 32:223–235
Bunker CH, Berson EL, Bromley WC et al (1984) Prevalence of retinitis pigmentosa in Maine. Am J Ophthalmol 97:357–365
Calvert PD, Strissel KJ, Schiesser WE et al (2006) Light-driven translocation of signaling proteins in vertebrate photoreceptors. Trends Cell Biol 16:560–568
Deretic D (2006) A role for rhodopsin in a signal transduction cascade that regulates membrane trafficking and photoreceptor polarity. Vision Res 46:4427–4433
Grossman GH, Pauer GJ, Narendra U et al (2009) Early synaptic defects in tulp1−/− mice. Invest Ophthalmol Vis Sci 50:3074–3083
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)
Gu S, Lennon A, Li Y et al (1998) Tubby-like protein-1 mutations in autosomal recessive retinitis pigmentosa. Lancet 351:1103–1104
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 18:174–176
Hagstrom SA, Duyao M, North MA et al (1999) Retinal degeneration in tulp1−/− mice: vesicular accumulation in the interphotoreceptor matrix. Invest Ophthalmol Vis Sci 40:2795–2802
Hagstrom SA, Adamian M, Scimeca M et al (2001) A role for the Tubby-like protein 1 in rhodopsin transport. Invest Ophthalmol Vis Sci 42:1955–1962
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 81:109–117
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 40:2706–2712
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 9:155–163
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 48:442–452
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 85:281–290
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 48:5160–5167
Nishina PM, North MA, Ikeda A et al (1998) Molecular characterization of a novel tubby gene family member, TULP3, in mouse and humans. Genomics 54:215–220
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 94:3128–3133
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 280:1248–1256
Paloma E, Hjelmqvist L, Bayes M et al (2000) Novel mutations in the TULP1 gene causing autosomal recessive retinitis pigmentosa. Invest Ophthalmol Vis Sci 41:656–659
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 7:1437–1447
Slepak VZ, Hurley JB (2008). Mechanism of light-induced translocation of arrestin and transducin in photoreceptors: interaction-restricted diffusion. IUBMB Life 60:2–9
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 46:4754–4761
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 48:2837–2844
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 19:5889–5897
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 104:8857–8862
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).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this paper
Cite this paper
Hagstrom, S.A., Watson, R.F., Pauer, G.J.T., Grossman, G.H. (2012). Tulp1 Is Involved in Specific Photoreceptor Protein Transport Pathways. In: LaVail, M., Ash, J., Anderson, R., Hollyfield, J., Grimm, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 723. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-0631-0_100
Download citation
DOI: https://doi.org/10.1007/978-1-4614-0631-0_100
Published:
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4614-0630-3
Online ISBN: 978-1-4614-0631-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)