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http://dx.doi.org/10.14348/molcells.2021.0027

Tsg101 Is Necessary for the Establishment and Maintenance of Mouse Retinal Pigment Epithelial Cell Polarity  

Le, Dai (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST))
Lim, Soyeon (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST))
Min, Kwang Wook (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST))
Park, Joon Woo (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST))
Kim, Youjoung (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST))
Ha, Taejeong (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST))
Moon, Kyeong Hwan (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST))
Wagner, Kay-Uwe (Department of Oncology, Wayne State University)
Kim, Jin Woo (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST))
Abstract
The retinal pigment epithelium (RPE) forms a monolayer sheet separating the retina and choroid in vertebrate eyes. The polarized nature of RPE is maintained by distributing membrane proteins differentially along apico-basal axis. We found the distributions of these proteins differ in embryonic, post-natal, and mature mouse RPE, suggesting developmental regulation of protein trafficking. Thus, we deleted tumor susceptibility gene 101 (Tsg101), a key component of endosomal sorting complexes required for transport (ESCRT), in embryonic and mature RPE to determine whether ESCRT-mediated endocytic protein trafficking correlated with the establishment and maintenance of RPE polarity. Loss of Tsg101 severely disturbed the polarity of RPE, which forms irregular aggregates exhibiting non-polarized distribution of cell adhesion proteins and activation of epidermal growth factor receptor signaling. These findings suggest that ESCRT-mediated protein trafficking is essential for the development and maintenance of RPE cell polarity.
Keywords
cell polarity; endosomal sorting complexes required for transport (ESCRT); retinal pigment epithelium (RPE); tumor susceptibility gene 101 (Tsg101);
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1 Finnemann, S.C., Bonilha, V.L., Marmorstein, A.D., and Rodriguez-Boulan, E. (1997). Phagocytosis of rod outer segments by retinal pigment epithelial cells requires alpha(v)beta5 integrin for binding but not for internalization. Proc. Natl. Acad. Sci. U. S. A. 94, 12932-12937.   DOI
2 Fujimura, N., Taketo, M.M., Mori, M., Korinek, V., and Kozmik, Z. (2009). Spatial and temporal regulation of Wnt/β-catenin signaling is essential for development of the retinal pigment epithelium. Dev. Biol. 334, 31-45.   DOI
3 Gallemore, R.P., Hughes, B.A., and Miller, S.S. (1997). Retinal pigment epithelial transport mechanisms and their contributions to the electroretinogram. Prog. Retin. Eye Res. 16, 509-566.   DOI
4 Grant, B.D. and Donaldson, J.G. (2009). Pathways and mechanisms of endocytic recycling. Nat. Rev. Mol. Cell Biol. 10, 597-608.   DOI
5 Gruenberg, J. and Stenmark, H. (2004). The biogenesis of multivesicular endosomes. Nat. Rev. Mol. Cell Biol. 5, 317-323.   DOI
6 Cachafeiro, M., Bemelmans, A.P., Samardzija, M., Afanasieva, T., Pournaras, J.A., Grimm, C., Kostic, C., Philippe, S., Wenzel, A., and Arsenijevic, Y. (2013). Hyperactivation of retina by light in mice leads to photoreceptor cell death mediated by VEGF and retinal pigment epithelium permeability. Cell Death Dis. 4, e781.   DOI
7 Gundersen, D., Orlowski, J., and Rodriguez-Boulan, E. (1991). Apical polarity of Na,K-ATPase in retinal pigment epithelium is linked to a reversal of the ankyrin-fodrin submembrane cytoskeleton. J. Cell Biol. 112, 863-872.   DOI
8 Hurley, J.H. (2010). The ESCRT complexes. Crit. Rev. Biochem. Mol. Biol. 45, 463-487.   DOI
9 Ha, T., Moon, K.H., Dai, L., Hatakeyama, J., Yoon, K., Park, H.S., Kong, Y.Y., Shimamura, K., and Kim, J.W. (2017). The retinal pigment epithelium is a Notch signaling niche in the mouse retina. Cell Rep. 19, 351-363.   DOI
10 Herz, H.M., Chen, Z., Scherr, H., Lackey, M., Bolduc, C., and Bergmann, A. (2006). vps25 mosaics display non-autonomous cell survival and overgrowth, and autonomous apoptosis. Development 133, 1871-1880.   DOI
11 Iacovelli, J., Zhao, C., Wolkow, N., Veldman, P., Gollomp, K., Ojha, P., Lukinova, N., King, A., Feiner, L., Esumi, N., et al. (2011). Generation of Cre transgenic mice with postnatal RPE-specific ocular expression. Invest. Ophthalmol. Vis. Sci. 52, 1378-1383.   DOI
12 Imamura, Y., Noda, S., Hashizume, K., Shinoda, K., Yamaguchi, M., Uchiyama, S., Shimizu, T., Mizushima, Y., Shirasawa, T., and Tsubota, K. (2006). Drusen, choroidal neovascularization, and retinal pigment epithelium dysfunction in SOD1-deficient mice: a model of age-related macular degeneration. Proc. Natl. Acad. Sci. U. S. A. 103, 11282-11287.   DOI
13 Kang, K.H., Lemke, G., and Kim, J.W. (2009). The PI3K-PTEN tug-of-war, oxidative stress and retinal degeneration. Trends Mol. Med. 15, 191-198.   DOI
14 Kim, J.W., Kang, K.H., Burrola, P., Mak, T.W., and Lemke, G. (2008). Retinal degeneration triggered by inactivation of PTEN in the retinal pigment epithelium. Genes Dev. 22, 3147-3157.   DOI
15 Martinez-Morales, J.R., Rodrigo, I., and Bovolenta, P. (2004). Eye development: a view from the retina pigmented epithelium. Bioessays 26, 766-777.   DOI
16 Kim, Y., Lim, S., Ha, T., Song, Y.H., Sohn, Y.I., Park, D.J., Paik, S.S., KimKaneyama, J.R., Song, M.R., Leung, A., et al. (2017). The LIM protein complex establishes a retinal circuitry of visual adaptation by regulating Pax6 alpha-enhancer activity. Elife 6, e21303.   DOI
17 Le Borgne, R. and Hoflack, B. (1998). Protein transport from the secretory to the endocytic pathway in mammalian cells. Biochim. Biophys. Acta 1404, 195-209.   DOI
18 Lehmann, G.L., Benedicto, I., Philp, N.J., and Rodriguez-Boulan, E. (2014). Plasma membrane protein polarity and trafficking in RPE cells: past, present and future. Exp. Eye Res. 126, 5-15.   DOI
19 Luzio, J.P., Piper, S.C., Bowers, K., Parkinson, M.D.J., Lehner, P.J., and Bright, N.A. (2009). ESCRT proteins and the regulation of endocytic delivery to lysosomes. Biochem. Soc. Trans. 37(Pt 1), 178-180.   DOI
20 Marmorstein, A.D. (2001). The polarity of the retinal pigment epithelium. Traffic 2, 867-872.   DOI
21 Mellman, I. and Nelson, W.J. (2008). Coordinated protein sorting, targeting and distribution in polarized cells. Nat. Rev. Mol. Cell Biol. 9, 833-845.   DOI
22 Moberg, K.H., Schelble, S., Burdick, S.K., and Hariharan, I.K. (2005). Mutations in erupted, the Drosophila ortholog of mammalian tumor susceptibility gene 101, elicit non-cell-autonomous overgrowth. Dev. Cell 9, 699-710.   DOI
23 Mori, M., Gargowitsch, L., Bornert, J.M., Garnier, J.M., Mark, M., Chambon, P., and Metzger, D. (2012). Temporally controlled targeted somatic mutagenesis in mouse eye pigment epithelium. Genesis 50, 828-832.   DOI
24 Mori, M., Metzger, D., Garnier, J.M., Chambon, P., and Mark, M. (2002). Site-specific somatic mutagenesis in the retinal pigment epithelium. Invest. Ophthalmol. Vis. Sci. 43, 1384-1388.
25 Shimura, M., Kakazu, Y., Oshima, Y., Tamai, M., and Akaike, N. (1999). Na+,K+-ATPase activity in cultured bovine retinal pigment epithelium. Invest. Ophthalmol. Vis. Sci. 40, 96-104.
26 Prusky, G.T., Alam, N.M., Beekman, S., and Douglas, R.M. (2004). Rapid quantification of adult and developing mouse spatial vision using a virtual optomotor system. Invest. Ophthalmol. Vis. Sci. 45, 4611-4616.   DOI
27 Rodriguez-Boulan, E. and Macara, I.G. (2014). Organization and execution of the epithelial polarity programme. Nat. Rev. Mol. Cell Biol. 15, 225-242.   DOI
28 Rowan, S. and Cepko, C.L. (2004). Genetic analysis of the homeodomain transcription factor Chx10 in the retina using a novel multifunctional BAC transgenic mouse reporter. Dev. Biol. 271, 388-402.   DOI
29 Saksena, S., Sun, J., Chu, T., and Emr, S.D. (2007). ESCRTing proteins in the endocytic pathway. Trends Biochem. Sci. 32, 561-573.   DOI
30 Schmidt, O. and Teis, D. (2012). The ESCRT machinery. Curr. Biol. 22, R116-R120.   DOI
31 Shivas, J.M., Morrison, H.A., Bilder, D., and Skop, A.R. (2010). Polarity and endocytosis: reciprocal regulation. Trends Cell Biol. 20, 445-452.   DOI
32 Simo, R., Villarroel, M., Corraliza, L., Hernandez, C., and Garcia-Ramirez, M. (2010). The retinal pigment epithelium: something more than a constituent of the blood-retinal barrier - implications for the pathogenesis of diabetic retinopathy. J. Biomed. Biotechnol. 2010, 190724.
33 Morita, E. (2012). Differential requirements of mammalian ESCRTs in multivesicular body formation, virus budding and cell division. FEBS J. 279, 1399-1406.   DOI
34 Soriano, P. (1999). Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat. Genet. 21, 70-71.   DOI
35 Strauss, O. (2005). The retinal pigment epithelium in visual function. Physiol. Rev. 85, 845-881.   DOI
36 Wagner, K.U., Krempler, A., Qi, Y., Park, K., Henry, M.D., Triplett, A.A., Riedlinger, G., Rucker III, E.B., and Hennighausen, L. (2003). Tsg101 is essential for cell growth, proliferation, and cell survival of embryonic and adult tissues. Mol. Cell. Biol. 23, 150-162.   DOI
37 Sztul, E.S., Biemesderfer, D., Caplan, M.J., Kashgarian, M., and Boyer, J.L. (1987). Localization of Na+,K+-ATPase alpha-subunit to the sinusoidal and lateral but not canalicular membranes of rat hepatocytes. J. Cell Biol. 104, 1239-1248.   DOI
38 Truschel, S.T., Simoes, S., Gangi Setty, S.R., Harper, D.C., Tenza, D., Thomas, P.C., Herman, K.E., Sackett, S.D., Cowan, D.C., Theos, A.C., et al. (2009). ESCRT-I function is required for Tyrp1 transport from early endosomes to the melanosome limiting membrane. Traffic 10, 1318-1336.   DOI
39 Vaccari, T. and Bilder, D. (2005). The Drosophila tumor suppressor vps25 prevents nonautonomous overproliferation by regulating notch trafficking. Dev. Cell 9, 687-698.   DOI
40 Veleri, S., Lazar, C.H., Chang, B., Sieving, P.A., Banin, E., and Swaroop, A. (2015). Biology and therapy of inherited retinal degenerative disease: insights from mouse models. Dis. Model. Mech. 8, 109-129.   DOI
41 Weisz, O.A. and Rodriguez-Boulan, E. (2009). Apical trafficking in epithelial cells: signals, clusters and motors. J. Cell Sci. 122, 4253-4266.   DOI
42 Williams, S.K., Greener, D.A., and Solenski, N.J. (1984). Endocytosis and exocytosis of protein in capillary endothelium. J. Cell. Physiol. 120, 157-162.   DOI
43 Xu, L., Overbeek, P.A., and Reneker, L.W. (2002). Systematic analysis of E-, N- and P-cadherin expression in mouse eye development. Exp. Eye Res. 74, 753-760.   DOI
44 Burke, J.M., Cao, F., Irving, P.E., and Skumatz, C.M.B. (1999). Expression of E-cadherin by human retinal pigment epithelium: delayed expression in vitro. Invest. Ophthalmol. Vis. Sci. 40, 2963-2970.
45 Adamson, E.D. and Rees, A.R. (1981). Epidermal growth factor receptors. Mol. Cell. Biochem. 34, 129-152.   DOI
46 Amerongen, H.M., Mack, J.A., Wilson, J.M., and Neutra, M.R. (1989). Membrane domains of intestinal epithelial cells: distribution of Na+, K+-ATPase and the membrane skeleton in adult rat intestine during fetal development and after epithelial isolation. J. Cell Biol. 109, 2129-2138.   DOI
47 Babst, M. (2011). MVB vesicle formation: ESCRT-dependent, ESCRT-independent and everything in between. Curr. Opin. Cell Biol. 23, 452-457.   DOI
48 Bakker, J., Spits, M., Neefjes, J., and Berlin, I. (2017). The EGFR odyssey - from activation to destruction in space and time. J. Cell Sci. 130, 4087-4096.   DOI
49 Bonilha, V.L., Finnemann, S.C., and Rodriguez-Boulan, E. (1999). Ezrin promotes morphogenesis of apical microvilli and basal infoldings in retinal pigment epithelium. J. Cell Biol. 147, 1533-1548.   DOI
50 Burke, J.M. and Hong, J. (2006). Fate of E-cadherin in early RPE cultures: transient accumulation of truncated peptides at nonjunctional sites. Invest. Ophthalmol. Vis. Sci. 47, 3635-3643.   DOI
51 Clague, M.J., Liu, H., and Urbe, S. (2012). Governance of endocytic trafficking and signaling by reversible ubiquitylation. Dev. Cell 23, 457-467.   DOI
52 Eden, E.R., White, I.J., and Futter, C.E. (2009). Down-regulation of epidermal growth factor receptor signalling within multivesicular bodies. Biochem. Soc. Trans. 37, 173-177.   DOI
53 Fang, D. and Setaluri, V. (1999). Role of microphthalmia transcription factor in regulation of melanocyte differentiation marker TRP-1. Biochem. Biophys. Res. Commun. 256, 657-663.   DOI