Rab8a vesicles regulate wnt ligand delivery and paneth cell maturation at the intestinal stem cell niche

Development (Cambridge)

Volumn 142, Issue 12, 2015, Pages 2147-2162

  Das, Soumyashree ^a   Yu, Shiyan ^a   Sakamori, Ryotaro ^a   Vedula, Pavan ^a   Feng, Qiang ^a   Flores, Juan ^a   Hoffman, Andrew ^b   Fu, Jiang ^c   Stypulkowski, Ewa ^a   Rodriguez, Alexis ^a   Dobrowolski, Radek ^a   Harada, Akihiro ^d   Hsu, Wei ^c   Bonder, Edward M ^a   Verzi, Michael P ^b,e   Gao, Nan ^a,e  

^a RUTGERS UNIVERSITY   (United States)

^b Life Sciences Building Rutgers University   (United States)

^c UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

^d OSAKA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^e RUTGERS CANCER INSTITUTE OF NEW JERSEY   (United States)

Author keywords

Gpr177; Intestinal stem cell; Paneth cell; Rab8a; Wnt secretion; Wntless

Indexed keywords

BETA CATENIN; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN 6; MEMBRANE PROTEIN; RAB8A PROTEIN; UNCLASSIFIED DRUG; WNT PROTEIN; G PROTEIN COUPLED RECEPTOR; GLYCOGEN SYNTHASE KINASE 3; GLYCOGEN SYNTHASE KINASE 3 BETA; GPR177 PROTEIN, MOUSE; HOMEODOMAIN PROTEIN; LGR5 PROTEIN, MOUSE; LRP6 PROTEIN, MOUSE; RAB PROTEIN; RAB8A PROTEIN, MOUSE; SIGNAL PEPTIDE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL MATURATION; CELL MEMBRANE; CELL SURFACE; CONTROLLED STUDY; IMMUNOGOLD LABELING; IN VITRO STUDY; INTESTINAL STEM CELL; INTESTINE CRYPT; MOUSE; NONHUMAN; PANETH CELL; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN PHOSPHORYLATION; PROTEIN SECRETION; REGULATORY MECHANISM; STEM CELL NICHE; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL CULTURE; CELL PROLIFERATION; CYTOLOGY; GENETICS; HUMAN; KNOCKOUT MOUSE; METABOLISM; PHOSPHORYLATION; PHYSIOLOGY; STEM CELL; TRANSCRIPTION INITIATION; WNT SIGNALING PATHWAY;

ANIMALS; BETA CATENIN; CELL PROLIFERATION; CELLS, CULTURED; GLYCOGEN SYNTHASE KINASE 3; HOMEODOMAIN PROTEINS; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; LOW DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN-6; MICE; MICE, KNOCKOUT; PANETH CELLS; PHOSPHORYLATION; RAB GTP-BINDING PROTEINS; RECEPTORS, G-PROTEIN-COUPLED; STEM CELL NICHE; STEM CELLS; TRANSCRIPTIONAL ACTIVATION; WNT PROTEINS; WNT SIGNALING PATHWAY;

EID: 84931043760     PISSN: 09501991     EISSN: 14779129     Source Type: Journal    
DOI: 10.1242/dev.121046     Document Type: Article

References (137)

1. Ang, A. L., Fölsch H., Koivisto, U.-M., Pypaert, M. and Mellman, I. (2003). The Rab8 GTPase selectively regulates AP-1B-dependent basolateral transport in polarized Madin-Darby canine kidney cells. J. Cell Biol. 163, 339-350
2. Angers, S. and Moon, R. T. (2009). Proximal events in Wnt signal transduction. Nat. Rev. Mol. Cell Biol. 10, 468-477
3. Bänziger, C., Soldini, D., Schütt C., Zipperlen, P., Hausmann, G. and Basler, K. (2006). Wntless, a conserved membrane protein dedicated to the secretion of Wnt proteins from signaling cells. Cell 125, 509-522
4. Barker, N., van Es, J. H., Kuipers, J., Kujala, P., van den Born, M., Cozijnsen, M., Haegebarth, A., Korving, J., Begthel, H., Peters, P. J. et al. (2007). Identification of stem cells in small intestine and colon by marker gene Lgr5 Nature 449, 1003-1007
5. Bartscherer, K., Pelte, N., Ingelfinger, D. and Boutros, M. (2006). Secretion of Wnt ligands requires Evi, a conserved transmembrane protein. Cell 125, 523-533
6. Belenkaya, T. Y., Wu, Y., Tang, X., Zhou, B., Cheng, L., Sharma, Y. V., Yan, D., Selva, E. M. and Lin, X. (2008). The retromer complex influences Wnt secretion by recycling wntless from endosomes to the trans-Golgi network. Dev. Cell 14, 120-131
7. Bilic, J., Huang, Y.-L., Davidson, G., Zimmermann, T., Cruciat, C.-M., Bienz, M. and Niehrs, C. (2007). Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation. Science 316, 1619-1622
8. Boehlke, C., Bashkurov, M., Buescher, A., Krick, T., John, A.-K., Nitschke, R., Walz, G. and Kuehn, E. W. (2010). Differential role of Rab proteins in ciliary trafficking: Rab23 regulates smoothened levels. J. Cell Sci. 123, 1460-1467
9. Boutros, M. and Mlodzik, M. (1999). Dishevelled: at the crossroads of divergent intracellular signaling pathways. Mech. Dev. 83, 27-37
10. Bryant, D. M., Datta, A., Rodrı́guez-Fraticelli A. E., Peränen J., Martı́n-Belmonte F. and Mostov, K. E. (2010). A molecular network for de novo generation of the apical surface and lumen. Nat. Cell Biol. 12, 1035-1045
11. Buczacki, S. J. A., Zecchini, H. I., Nicholson, A. M., Russell, R., Vermeulen, L., Kemp, R. and Winton, D. J. (2013). Intestinal label-retaining cells are secretory precursors expressing Lgr5 Nature 495, 65-69
12. Cadigan, K. M. and Peifer, M. (2009). Wnt signaling from development to disease: insights from model systems. Cold Spring Harb. Perspect. Biol. 1, a002881
13. Charng, W.-L., Yamamoto, S., Jaiswal, M., Bayat, V., Xiong, B., Zhang, K., Sandoval, H., David, G., Gibbs, S., Lu, H.-C. et al. (2014). Drosophila Tempura, a novel protein prenyltransferase alpha subunit, regulates notch signaling via Rab1 and Rab11 PLoS Biol. 12, e1001777
14. Chen, B., Dodge, M. E., Tang, W., Lu, J., Ma, Z., Fan, C.-W., Wei, S., Hao, W., Kilgore, J., Williams, N. S. et al. (2009). Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. Nat. Chem. Biol. 5, 100-107
15. Chi, S., Xie, G., Liu, H., Chen, K., Zhang, X., Li, C. and Xie, J. (2012). Rab23 negatively regulates Gli1 transcriptional factor in a Su(Fu)-dependent manner. Cell Signal. 24, 1222-1228
16. Ching, W. and Nusse, R. (2006). A dedicated Wnt secretion factor. Cell 125, 432-433
17. Clarke, A. R. (2006). Wnt signalling in the mouse intestine. Oncogene 25, 7512-7521
18. Clevers, H. (2006). Wnt/beta-catenin signaling in development and disease. Cell 127, 469-480
19. Clevers, H. and Nusse, R. (2012). Wnt/β-catenin signaling and disease. Cell 149, 1192-1205
20. Clevers, H., Loh, K. M. and Nusse, R. (2014). An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control. Science 346, 1248012
21. Das, A. and Guo, W. (2011). Rabs and the exocyst in ciliogenesis, tubulogenesis and beyond. Trends Cell Biol. 21, 383-386
22. Das, S., Yu, S., Sakamori, R., Stypulkowski, E. and Gao, N. (2012). Wntless in Wnt secretion: molecular, cellular and genetic aspects. Front. Biol. (Beijing) 7, 587-593.
23. de Groot, R. E. A., Farin, H. F., Macůrková, M., van Es, J. H., Clevers, H. C. and Korswagen, H. C. (2013). Retromer dependent recycling of the Wnt secretion factor Wls is dispensable for stem cell maintenance in the mammalian intestinal epithelium. PLoS ONE 8, e76971.
24. de Lau, W., Barker, N. and Clevers, H. (2007). WNT signaling in the normal intestine and colorectal cancer. Front. Biosci. 12, 471-491
25. Demir, K., Kirsch, N., Beretta, C. A., Erdmann, G., Ingelfinger, D., Moro, E., Argenton, F., Carl, M., Niehrs, C. and Boutros, M. (2013). RAB8B is required for activity and caveolar endocytosis of LRP6. Cell Rep. 4, 1224-1234
26. Dong, C., Yang, L., Zhang, X., Gu, H., Lam, M. L., Claycomb, W. C., Xia, H. and Wu, G. (2010). Rab8 interacts with distinct motifs in alpha2B- and beta2- adrenergic receptors and differentially modulates their transport. J. Biol. Chem. 285, 20369-20380
27. Durand, A., Donahue, B., Peignon, G., Letourneur, F., Cagnard, N., Slomianny, C., Perret, C., Shroyer, N. F. and Romagnolo, B. (2012). Functional intestinal stem cells after Paneth cell ablation induced by the loss of transcription factor Math1 (Atoh1). Proc. Natl. Acad. Sci. USA 109, 8965-8970
28. Eaton, S. (2008). Retromer retrieves wntless. Dev. Cell 14, 4-6
29. Eaton, S., Wepf, R. and Simons, K. (1996). Roles for Rac1 and Cdc42 in planar polarization and hair outgrowth in the wing of Drosophila. J. Cell Biol. 135, 1277-1289
30. Eggenschwiler, J. T., Espinoza, E. and Anderson, K. V. (2001). Rab23 is an essential negative regulator of the mouse Sonic hedgehog signalling pathway. Nature 412, 194-198
31. Emery, G., Hutterer, A., Berdnik, D., Mayer, B., Wirtz-Peitz, F., Gaitan, M. G. and Knoblich, J. A. (2005). Asymmetric Rab11 endosomes regulate delta recycling and specify cell fate in the Drosophila nervous system. Cell 122, 763-773
32. Esseltine, J. L., Ribeiro, F. M. and Ferguson, S. S. G. (2012). Rab8 modulates metabotropic glutamate receptor subtype 1 intracellular trafficking and signaling in a protein kinase C-dependent manner. J. Neurosci. 32, 16933-16942
33. Evans, T. M., Ferguson, C., Wainwright, B. J., Parton, R. G. and Wicking, C. (2003). Rab23, a negative regulator of hedgehog signaling, localizes to the plasma membrane and the endocytic pathway. Traffic 4, 869-884
34. Fanto, M., Weber, U., Strutt, D. I. and Mlodzik, M. (2000). Nuclear signaling by Rac and Rho GTPases is required in the establishment of epithelial planar polarity in the Drosophila eye. Curr.Biol. 10, 979-988
35. Farin, H. F., Van Es, J. H. and Clevers, H. (2012). Redundant sources of Wnt regulate intestinal stem cells and promote formation of Paneth cells. Gastroenterology 143, 1518-1529.e7
36. Feng, Q. and Gao, N. (2014). Keeping Wnt signalosome in check by vesicular traffic. J. Cell. Physiol. 230, 1170-1180
37. Franch-Marro, X., Wendler, F., Guidato, S., Griffith, J., Baena-Lopez, A., Itasaki, N., Maurice, M. M. and Vincent, J.-P. (2008). Wingless secretion requires endosome-to-Golgi retrieval ofWntless/Evi/Sprinter by the retromer complex. Nat.Cell Biol. 10, 170-177
38. Fu, J., Jiang, M., Mirando, A. J., Yu, H.-M. I. and Hsu, W. (2009). Reciprocal regulation of Wnt and Gpr177/mouse Wntless is required for embryonic axis formation. Proc. Natl. Acad. Sci. USA 106, 18598-18603
39. Fu, J., Ivy Yu, H.-M., Maruyama, T., Mirando, A. J. and Hsu, W. (2011). Gpr177/ mouse Wntless is essential for Wnt-mediated craniofacial and brain development. Dev. Dyn. 240, 365-371
40. Galliot, B. (2013). Injury-induced asymmetric cell death as a driving force for head regeneration in Hydra. Dev. Genes Evol. 223, 39-52
41. Gao, N. and Kaestner, K. H. (2010). Cdx2 regulates endo-lysosomal function and epithelial cell polarity. Genes Dev. 24, 1295-1305
42. Gao, N., White, P. and Kaestner, K. H. (2009). Establishment of intestinal identity and epithelial-mesenchymal signaling by Cdx2 Dev. Cell 16, 588-599
43. Gao, N., Davuluri, G., Gong, W., Seiler, C., Lorent, K., Furth, E. E., Kaestner, K. H. and Pack, M. (2011). The nuclear pore complex protein Elys is required for genome stability in mouse intestinal epithelial progenitor cells. Gastroenterology 140, 1547-1555
44. Gasnereau, I., Herr, P., Chia, P. Z. C., Basler, K. and Gleeson, P. A. (2011). Identification of an endocytosis motif in an intracellular loop of Wntless protein, essential for its recycling and the control of Wnt protein signaling. J. Biol. Chem. 286, 43324-43333
45. Gerges, N. Z., Backos, D. S. and Esteban, J. A. (2004). Local control of AMPA receptor trafficking at the postsynaptic terminal by a small GTPase of the Rab family. J. Biol. Chem. 279, 43870-43878
46. Goel, S., Chin, E. N., Fakhraldeen, S. A., Berry, S. M., Beebe, D. J. and Alexander, C. M. (2012). Both LRP5 and LRP6 receptors are required to respond to physiological Wnt ligands in mammary epithelial cells and fibroblasts. J. Biol. Chem. 287, 16454-16466
47. Goldenring, J. R. (2013). A central role for vesicle trafficking in epithelial neoplasia: intracellular highways to carcinogenesis. Nat. Rev. Cancer 13, 813-820
48. Gregorieff, A. and Clevers, H. (2005). Wnt signaling in the intestinal epithelium: from endoderm to cancer. Genes Dev. 19, 877-890
49. Gregorieff, A., Pinto, D., Begthel, H., Destree, O., Kielman, M. and Clevers, H. (2005). Expression pattern of Wnt signaling components in the adult intestine. Gastroenterology 129, 626-638
50. Habas, R., Kato, Y. and He, X. (2001). Wnt/Frizzled activation of Rho regulates vertebrate gastrulation and requires a novel Formin homology protein Daam1 Cell 107, 843-854
51. Habas, R., Dawid, I. B. and He, X. (2003). Coactivation of Rac and Rho by Wnt/ Frizzled signaling is required for vertebrate gastrulation. Genes Dev. 17, 295-309
52. Haegebarth, A. and Clevers, H. (2009). Wnt signaling, Lgr5, and stem cells in the intestine and skin. Am. J. Pathol. 174, 715-721
53. Harterink, M., Port, F., Lorenowicz, M. J., McGough, I. J., Silhankova, M., Betist, M. C., van Weering, J. R. T., van Heesbeen, R. G. H. P., Middelkoop, T. C., Basler, K. et al. (2011). A SNX3-dependent retromer pathway mediates retrograde transport of the Wnt sorting receptor Wntless and is required for Wnt secretion. Nat. Cell Biol. 13, 914-923
54. Hattula, K., Furuhjelm, J., Tikkanen, J., Tanhuanpaa, K., Laakkonen, P. and Peranen, J. (2006). Characterization of the Rab8-specific membrane traffic route linked to protrusion formation. J. Cell Sci. 119, 4866-4877
55. He, X., Saint-Jeannet, J.-P., Wang, Y., Nathans, J., Dawid, I. and Varmus, H. (1997). A member of the Frizzled protein family mediating axis induction by Wnt- 5A. Science 275, 1652-1654
56. He, X., Semenov, M., Tamai, K. and Zeng, X. (2004). LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the way. Development 131, 1663-1677
57. Henry, L. and Sheff, D. R. (2008). Rab8 regulates basolateral secretory, but not recycling, traffic at the recycling endosome. Mol. Biol. Cell 19, 2059-2068
58. Hong, W. and Tang, B. L. (1993). Protein trafficking along the exocytotic pathway. Bioessays 15, 231-238
59. Huang, H. and He, X. (2008). Wnt/beta-catenin signaling: new (and old) players and new insights. Curr. Opin. Cell Biol. 20, 119-125
60. Huber, L. A., de Hoop, M. J., Dupree, P., Zerial, M., Simons, K. and Dotti, C. (1993a). Protein transport to the dendritic plasma membrane of cultured neurons is regulated by rab8p. J. Cell Biol. 123, 47-55
61. Huber, L. A., Pimplikar, S., Parton, R. G., Virta, H., Zerial, M. and Simons, K. (1993b). Rab8, a small GTPase involved in vesicular traffic between the TGN and the basolateral plasma membrane. J. Cell Biol. 123, 35-45
62. Hume, A. N., Collinson, L. M., Rapak, A., Gomes, A. Q., Hopkins, C. R. and Seabra, M. C. (2001). Rab27a regulates the peripheral distribution of melanosomes in melanocytes. J. Cell Biol. 152, 795-808
63. Hutagalung, A. H. and Novick, P. J. (2011). Role of Rab GTPases in membrane traffic and cell physiology. Physiol. Rev. 91, 119-149
64. Jiang, M., Ku, W.-Y., Fu, J., Offermanns, S., Hsu, W. and Que, J. (2013). Gpr177 regulates pulmonary vasculature development. Development 140, 3589-3594
65. Kabiri, Z., Greicius, G., Madan, B., Biechele, S., Zhong, Z., Zaribafzadeh, H., Edison, Aliyev, J., Wu, Y., Bunte, R. et al. (2014). Stroma provides an intestinal stem cell niche in the absence of epithelial Wnts. Development 141, 2206-2215
66. Khandelwal, P., Prakasam, H. S., Clayton, D. R., Ruiz, W. G., Gallo, L. I., van Roekel, D., Lukianov, S., Peranen, J., Goldenring, J. R. and Apodaca, G. (2013). A Rab11a-Rab8a-Myo5B network promotes stretch-regulated exocytosis in bladder umbrella cells. Mol. Biol. Cell 24, 1007-1019
67. Kim, T.-H., Escudero, S. and Shivdasani, R. A. (2012). Intact function of Lgr5 receptor-expressing intestinal stem cells in the absence of Paneth cells. Proc. Natl. Acad. Sci. USA 109, 3932-3937
68. Knowles, B. C., Weis, V. G., Yu, S., Roland, J. T., Williams, J. A., Alvarado, G. S., Lapierre, L. A., Shub, M. D., Gao, N. and Goldenring, J. R. (2015). Rab11a regulates Syntaxin 3 localization and microvillus assembly in enterocytes. J.Cell Sci. (in press) pii: jcs.163303
69. Kremer, J. R., Mastronarde, D. N. and McIntosh, J. R. (1996). Computer visualization of three-dimensional image data using IMOD. J. Struct. Biol. 116, 71-76
70. Kuhnert, F., Davis, C. R., Wang, H.-T., Chu, P., Lee, M., Yuan, J., Nusse, R. and Kuo, C. J. (2004). Essential requirement for Wnt signaling in proliferation of adult small intestine and colon revealed by adenoviral expression of Dickkopf-1. Proc.Natl.Acad.Sci.USA 101, 266-271
71. Lim, X., Tan, S. H., Koh, W. L. C., Chau, R. M. W., Yan, K. S., Kuo, C. J., van Amerongen, R., Klein, A. M. and Nusse, R. (2013). Interfollicular epidermal stem cells self-renew via autocrine Wnt signaling. Science 342, 1226-1230
72. Lustig, B., Jerchow, B., Sachs, M., Weiler, S., Pietsch, T., Karsten, U., van de Wetering, M., Clevers, H., Schlag, P. M., Birchmeier, W. et al. (2002). Negative feedback loop of Wnt signaling through upregulation of conductin/axin2 in colorectal and liver tumors. Mol. Cell. Biol. 22, 1184-1193
73. Ma, Y., Erkner, A., Gong, R., Yao, S., Taipale, J., Basler, K. and Beachy, P. A. (2002). Hedgehog-mediated patterning of the mammalian embryo requires transporter-like function of dispatched. Cell 111, 63-75
74. MacDonald, B. T. and He, X. (2012). Frizzled and LRP5/6 receptors for Wnt/β- catenin signaling. Cold Spring Harb. Perspect. Biol. 4, a007880
75. MacDonald, B. T., Tamai, K. and He, X. (2009). Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev. Cell 17, 9-26
76. Markova, S. V., Golz, S., Frank, L. A., Kalthof, B. and Vysotski, E. S. (2004). Cloning and expression of cDNA for a luciferase from the marine copepod Metridia longa: A novel secreted bioluminescent reporter enzyme. J. Biol. Chem. 279, 3212-3217
77. Mastronarde, D. N. (2005). Automated electron microscope tomography using robust prediction of specimen movements. J. Struct. Biol. 152, 36-51
78. Meijering, E., Dzyubachyk, O. and Smal, I. (2012). Methods for cell and particle tracking. Methods Enzymol. 504, 183-200
79. Mikels, A. J. and Nusse, R. (2006). PurifiedWnt5a protein activates or inhibits betacatenin- TCF signaling depending on receptor context. PLoS Biol. 4, e115
80. Miyoshi, H., Ajima, R., Luo, C. T., Yamaguchi, T. P. and Stappenbeck, T. S. (2012). Wnt5a potentiates TGF-beta signaling to promote colonic crypt regeneration after tissue injury. Science 338, 108-113
81. Montgomery, R. K., Carlone, D. L., Richmond, C. A., Farilla, L., Kranendonk, M. E. G., Henderson, D. E., Baffour-Awuah, N. Y., Ambruzs, D. M., Fogli, L. K., Algra, S. et al. (2011). Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells. Proc. Natl. Acad. Sci. USA 108, 179-184
82. Muñoz, J., Stange, D. E., Schepers, A. G., van de Wetering, M., Koo, B.-K., Itzkovitz, S., Volckmann, R., Kung, K. S., Koster, J., Radulescu, S. et al. (2012). The Lgr5 intestinal stem cell signature: robust expression of proposed quiescent ‘+4’ cell markers. EMBO J. 31, 3079-3091
83. Nusse, R., Fuerer, C., Ching, W., Harnish, K., Logan, C., Zeng, A., ten Berge, D. and Kalani, Y. (2008). Wnt signaling and stem cell control. Cold Spring Harb.Symp.Quant. iol. 73, 59-66
84. Okamoto, M., Udagawa, N., Uehara, S., Maeda, K., Yamashita, T., Nakamichi, Y., Kato, H., Saito, N., Minami, Y., Takahashi, N. et al. (2014). Noncanonical Wnt5a enhances Wnt/beta-catenin signaling during osteoblastogenesis. Sci. Rep. 4, 4493
85. Pan, C.-L., Baum, P. D., Gu, M., Jorgensen, E. M., Clark, S. G. and Garriga, G. (2008). C. elegans AP-2 and retromer control Wnt signaling by regulating mig-14/Wntless. Dev. Cell 14, 132-139
86. Pinto, D., Gregorieff, A., Begthel, H. and Clevers, H. (2003). Canonical Wnt signals are essential for homeostasis of the intestinal epithelium. Genes Dev. 17, 1709-1713
87. Polakis, P. (2007). The many ways of Wnt in cancer. Curr. Opin. Genet. Dev. 17, 45-51
88. Port, F. and Basler, K. (2010). Wnt trafficking: new insights into Wnt maturation, secretion and spreading. Traffic 11, 1265-1271
89. Port, F., Kuster, M., Herr, P., Furger, E., Bänziger, C., Hausmann, G. and Basler, K. (2008). Wingless secretion promotes and requires retromer-dependent cycling of Wntless. Nat.Cell Biol. 10, 178-185
90. Powell, A. E., Wang, Y., Li, Y., Poulin, E. J., Means, A. L., Washington, M. K., Higginbotham, J. N., Juchheim, A., Prasad, N., Levy, S. E. et al. (2012). The pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that functions as a tumor suppressor. Cell 149, 146-158
91. Reya, T. and Clevers, H. (2005). Wnt signalling in stem cells and cancer. Nature 434, 843-850
92. Rodriguez, O. C. and Cheney, R. E. (2002). Human myosin-Vc is a novel class V myosin expressed in epithelial cells. J. Cell Sci. 115, 991-1004
93. Roelink, H. and Nusse, R. (1991). Expression of two members of the Wnt family during mouse development–restricted temporal and spatial patterns in the developing neural tube. Genes Dev. 5, 381-388
94. Rojas, R., van Vlijmen, T., Mardones, G. A., Prabhu, Y., Rojas, A. L., Mohammed, S., Heck, A. J. R., Raposo, G., van der Sluijs, P. and Bonifacino, J. S. (2008). Regulation of retromer recruitment to endosomes by sequential action of Rab5 and Rab7. J.Cell Biol. 183, 513-526
95. Roland, J. T., Lapierre, L. A. and Goldenring, J. R. (2009). Alternative splicing in class V myosins determines association with Rab10. J.Biol.Chem. 284, 1213-1223
96. Roland, J. T., Bryant, D. M., Datta, A., Itzen, A., Mostov, K. E. and Goldenring, J. R. (2011). Rab GTPase-Myo5B complexes control membrane recycling and epithelial polarization. Proc. Natl. Acad. Sci. USA 108, 2789–2794
97. Roth, S., Franken, P., Sacchetti, A., Kremer, A., Anderson, K., Sansom, O. and Fodde, R. (2012). Paneth cells in intestinal homeostasis and tissue injury. PLoS ONE 7, e38965
98. Sakamori, R., Das, S., Yu, S., Feng, S., Stypulkowski, E., Guan, Y., Douard, V., Tang, W., Ferraris, R. P., Harada, A. et al. (2012). Cdc42 and Rab8a are critical for intestinal stem cell division, survival, and differentiation in mice. J. Clin. Invest. 122, 1052-1065
99. Sakamori, R., Yu, S., Zhang, X., Hoffman, A., Sun, J., Das, S., Vedula, P., Li, G., Fu, J., Walker, F. et al. (2014). CDC42 inhibition suppresses progression of incipient intestinal tumors. Cancer Res. 74, 5480-5492
100. San Roman, A. K., Jayewickreme, C. D., Murtaugh, L. C. and Shivdasani, R. A. (2014). Wnt secretion from epithelial cells and subepithelial myofibroblasts is not required in the mouse intestinal stem cell niche in vivo. Stem Cell Rep. 2, 127-134
101. Sangiorgi, E. and Capecchi, M. R. (2008). Bmi1 is expressed in vivo in intestinal stem cells. Nat. Genet. 40, 915-920
102. Sato, N., Meijer, L., Skaltsounis, L., Greengard, P. and Brivanlou, A. H. (2004). Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor. Nat. Med. 10, 55-63
103. Sato, T., Mushiake, S., Kato, Y., Sato, K., Sato, M., Takeda, N., Ozono, K., Miki, K., Kubo, Y., Tsuji, A. et al. (2007). The Rab8 GTPase regulates apical protein localization in intestinal cells. Nature 448, 366-369
104. Sato, T., Vries, R. G., Snippert, H. J., van de Wetering, M., Barker, N., Stange, D. E., van Es, J. H., Abo, A., Kujala, P., Peters, P. J. et al. (2009). Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459, 262-265
105. Sato, T., van Es, J. H., Snippert, H. J., Stange, D. E., Vries, R. G., van den Born, M., Barker, N., Shroyer, N. F., van de Wetering, M. and Clevers, H. (2011). Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 469, 415-418
106. Sato, T., Iwano, T., Kunii, M., Matsuda, S., Mizuguchi, R., Jung, Y., Hagiwara, H., Yoshihara, Y., Yuzaki, M., Harada, R. et al. (2014). Rab8a and Rab8b are essential for several apical transport pathways but insufficient for ciliogenesis. J. Cell Sci. 127, 422-431
107. Schulte, G. (2010). International union of basic and clinical pharmacology. LXXX. The class Frizzled receptors. Pharmacol. Rev. 62, 632-667
108. Schulte, G. and Bryja, V. (2007). The Frizzled family of unconventional G-proteincoupled receptors. Trends Pharmacol. Sci. 28, 518-525
109. Seabra, M. C., Mules, E. H. and Hume, A. N. (2002). Rab GTPases, intracellular traffic and disease. Trends Mol. Med. 8, 23-30
110. Stefater, J. A., Lewkowich, I., Rao, S., Mariggi, G., Carpenter, A. C., Burr, A. R., Fan, J., Ajima, R., Molkentin, J. D., Williams, B. O. et al. (2011). Regulation of angiogenesis by a non-canonical Wnt-Flt1 pathway in myeloid cells. Nature 474, 511-515
111. Strutt, D. I., Weber, U. and Mlodzik, M. (1997). The role of RhoA in tissue polarity and Frizzled signalling. Nature 387, 292-295
112. Sun, Y., Chiu, T. T., Foley, K. P., Bilan, P. J. and Klip, A. (2014). Myosin Va mediates Rab8A-regulated GLUT4 vesicle exocytosis in insulin-stimulated muscle cells. Mol. Biol. Cell 25, 1159-1170
113. Takada, R., Satomi, Y., Kurata, T., Ueno, N., Norioka, S., Kondoh, H., Takao, T. and Takada, S. (2006). Monounsaturated fatty acid modification of Wnt protein: its role in Wnt secretion. Dev. Cell 11, 791-801
114. Takeda, N., Jain, R., LeBoeuf, M. R., Wang, Q., Lu, M. M. and Epstein, J. A. (2011). Interconversion between intestinal stem cell populations in distinct niches. Science 334, 1420-1424
115. Tamai, K., Semenov, M., Kato, Y., Spokony, R., Liu, C., Katsuyama, Y., Hess, F., Saint-Jeannet, J.-P. and He, X. (2000). LDL-receptor-related proteins in Wnt signal transduction. Nature 407, 530-535
116. Tanaka, K., Kitagawa, Y. and Kadowaki, T. (2002). Drosophila segment polarity gene product porcupine stimulates the posttranslational N-glycosylation of wingless in the endoplasmic reticulum. J. Biol. Chem. 277, 12816-12823
117. Tetteh, P. W., Farin, H. F. and Clevers, H. (2014). Plasticity within stem cell hierarchies in mammalian epithelia. Trends Cell Biol. 25, 100-108
118. Tian, H., Biehs, B., Warming, S., Leong, K. G., Rangell, L., Klein, O. D. and de Sauvage, F. J. (2011). A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature 478, 255-259.
119. van deWetering, M., Sancho, E., Verweij, C., de Lau, W., Oving, I., Hurlstone, A., van der Horn, K., Batlle, E., Coudreuse, D., Haramis, A.-P. et al. (2002). The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell 111, 241-250.
120. van Es, J. H., Jay, P., Gregorieff, A., van Gijn, M. E., Jonkheer, S., Hatzis, P., Thiele, A., van den Born, M., Begthel, H., Brabletz, T. et al. (2005). Wnt signalling induces maturation of Paneth cells in intestinal crypts. Nat. Cell Biol. 7, 381-386.
121. van Es, J. H., Sato, T., van de Wetering, M., Lyubimova, A., Yee Nee, A. N., Gregorieff, A., Sasaki, N., Zeinstra, L., van den Born, M., Korving, J. et al. (2012). Dll1(+) secretory progenitor cells revert to stem cells upon crypt damage. Nat.Cell Biol. 14, 1099-1104
122. Wallingford, J. B. and Habas, R. (2005). The developmental biology of Dishevelled: an enigmatic protein governing cell fate and cell polarity. Development 132, 4421-4436
123. Wang, G. and Wu, G. (2012). Small GTPase regulation of GPCR anterograde trafficking. Trends Pharmacol. Sci. 33, 28-34
124. Wehrli, M., Dougan, S. T., Caldwell, K., O’Keefe, L., Schwartz, S., Vaizel- Ohayon, D., Schejter, E., Tomlinson, A. and DiNardo, S. (2000). arrowencodes an LDL-receptor-related protein essential for Wingless signalling. Nature 407, 527-530
125. Willert, K. and Nusse, R. (2012). Wnt proteins. Cold Spring Harb. Perspect. Biol. 4, a007864
126. Willert, K., Brown, J. D., Danenberg, E., Duncan, A.W., Weissman, I. L., Reya, T., Yates, J. R. and Nusse, R. (2003). Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature 423, 448-452
127. Wong, H.-C., Bourdelas, A., Krauss, A., Lee, H.-J., Shao, Y., Wu, D., Mlodzik, M., Shi, D.-L. and Zheng, J. (2003). Direct binding of the PDZ domain of Dishevelled to a conserved internal sequence in the C-terminal region of Frizzled. Mol. Cell 12, 1251-1260
128. Wong, V.W. Y., Stange, D. E., Page, M. E., Buczacki, S., Wabik, A., Itami, S., van deWetering, M., Poulsom, R., Wright, N. A., Trotter, M.W. B. et al. (2012). Lrig1 controls intestinal stem-cell homeostasis by negative regulation of ErbB signalling. Nat. Cell Biol. 14, 401-408
129. Wu, C.-h. and Nusse, R. (2002). Ligand receptor interactions in the Wnt signaling pathway in Drosophila. J. Biol. Chem. 277, 41762-41769
130. Wu, X., Bowers, B., Rao, K., Wei, Q. and Hammer, J. A.III (1998). Visualization of melanosome dynamics within wild-type and dilute melanocytes suggests a paradigm for myosin V function In vivo. J. Cell Biol. 143, 1899-1918
131. Yan, K. S., Chia, L. A., Li, X., Ootani, A., Su, J., Lee, J. Y., Su, N., Luo, Y., Heilshorn, S. C., Amieva, M. R. et al. (2012). The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations. Proc. Natl. Acad. Sci. USA 109, 466-471
132. Yang, P.-T., Lorenowicz, M. J., Silhankova, M., Coudreuse, D. Y. M., Betist, M. C. and Korswagen, H. C. (2008). Wnt signaling requires retromer-dependent recycling of MIG-14/Wntless in Wnt-producing cells. Dev. Cell 14, 140-147
133. Yin, X., Farin, H. F., van Es, J. H., Clevers, H., Langer, R. and Karp, J. M. (2014). Niche-independent high-purity cultures of Lgr5(+) intestinal stem cells and their progeny. Nat. Methods 11, 106-112
134. Yu, H.-M. I., Jin, Y., Fu, J. and Hsu, W. (2010). Expression of Gpr177, a Wnt trafficking regulator, in mouse embryogenesis. Dev. Dyn. 239, 2102-2109
135. Yu, J., Chia, J., Canning, C. A., Jones, C. M., Bard, F. A. and Virshup, D. M. (2014a). WLS retrograde transport to the endoplasmic reticulum during Wnt secretion. Dev. Cell 29, 277-291
136. Yu, S., Nie, Y., Knowles, B., Sakamori, R., Stypulkowski, E., Patel, C., Das, S., Douard, V., Ferraris, R. P., Bonder, E. M. et al. (2014b). TLR sorting by Rab11 endosomes maintains intestinal epithelial-microbial homeostasis. EMBO J. 33, 1882-1895
137. Yu, S., Yehia, G., Wang, J., Stypulkowski, E., Sakamori, R., Jiang, P., Hernandez-Enriquez, B., Tran, T. S., Bonder, E. M., Guo, W. et al. (2014c). Global ablation of the mouse rab11a gene impairs early embryogenesis and matrix metalloproteinase secretion. J. Biol. Chem. 289, 32030-32043.