Original Article

Rab11 Regulates the Compartmentalization of Early Endosomes Required for Efficient Transport from Early Endosomes to the trans-Golgi Network

Correspondence to: Mona Wilcke, Molecular Biology and Genomics, Department of Biology, Pharmacia Corporation, S-112 87 Stockholm, Sweden. Tel:46-8-6958610 Fax:46-8-6185882 E-mail:mona.wilcke{at}eu.pnu.com.

Several GTPases of the Rab family, known to be regulators of membrane traffic between organelles, have been described and localized to various intracellular compartments. Rab11 has previously been reported to be associated with the pericentriolar recycling compartment, post-Golgi vesicles, and the trans-Golgi network (TGN). We compared the effect of overexpression of wild-type and mutant forms of Rab11 on the different intracellular transport steps in the endocytic/degradative and the biosynthetic/exocytic pathways in HeLa cells. We also studied transport from endosomes to the Golgi apparatus using the Shiga toxin B subunit (STxB) and TGN38 as reporter molecules. Overexpression of both Rab11 wild-type (Rab11wt) and mutants altered the localization of the transferrrin receptor (TfR), internalized Tf, the STxB, and TGN38. In cells overexpressing Rab11wt and in a GTPase-deficient Rab11 mutant (Rab11Q70L), these proteins were found in vesicles showing characteristics of sorting endosomes lacking cellubrevin (Cb). In contrast, they were redistributed into an extended tubular network, together with Cb, in cells overexpressing a dominant negative mutant of Rab11 (Rab11S25N). This tubularized compartment was not accessible to Tf internalized at temperatures <20°C, suggesting that it is of recycling endosomal origin. Overexpression of Rab11wt, Rab11Q70L, and Rab11S25N also inhibited STxB and TGN38 transport from endosomes to the TGN. These results suggest that Rab11 influences endosome to TGN trafficking primarily by regulating membrane distribution inside the early endosomal pathway.

Key Words: Rab11, intracellular trafficking, endosomes, Shiga toxin, TGN38

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• Inaba, T., Nagano, Y., Nagasaki, T., Sasaki, Y. (2002). Distinct Localization of Two Closely Related Ypt3/Rab11 Proteins on the Trafficking Pathway in Higher Plants. J. Biol. Chem. 277: 9183-9188 [Abstract] [Full Text]  
• Mallard, F., Tang, B. L., Galli, T., Tenza, D., Saint-Pol, A., Yue, X., Antony, C., Hong, W., Goud, B., Johannes, L. (2002). Early/recycling endosomes-to-TGN transport involves two SNARE complexes and a Rab6 isoform. JCB 156: 653-664 [Abstract] [Full Text]  
• Perez, F., Pernet-Gallay, K., Nizak, C., Goodson, H. V., Kreis, T. E., Goud, B. (2002). CLIPR-59, a new trans-Golgi/TGN cytoplasmic linker protein belonging to the CLIP-170 family. JCB 156: 631-642 [Abstract] [Full Text]  
• Lauvrak, S. U., Llorente, A., Iversen, T.-G., Sandvig, K. (2002). Selective regulation of the Rab9-independent transport of ricin to the Golgi apparatus by calcium. J. Cell Sci. 115: 3449-3456 [Abstract] [Full Text]  
• Tarabal, O., Caldero, J., Llado, J., Oppenheim, R. W., Esquerda, J. E. (2001). Long-Lasting Aberrant Tubulovesicular Membrane Inclusions Accumulate in Developing Motoneurons after a Sublethal Excitotoxic Insult: A Possible Model for Neuronal Pathology in Neurodegenerative Disease. J. Neurosci. 21: 8072-8081 [Abstract] [Full Text]  
• Prekeris, R., Davies, J. M., Scheller, R. H. (2001). Identification of a Novel Rab11/25 Binding Domain Present in Eferin and Rip Proteins. J. Biol. Chem. 276: 38966-38970 [Abstract] [Full Text]  
• Segev, N. (2001). Ypt/Rab GTPases: Regulators of Protein Trafficking. Sci Signal 2001: re11-re11 [Abstract] [Full Text]  
• Mallard, F., Tang, B. L., Galli, T., Tenza, D., Saint-Pol, A., Yue, X., Antony, C., Hong, W., Goud, B., Johannes, L. (2002). Early/recycling endosomes-to-TGN transport involves two SNARE complexes and a Rab6 isoform. JCB 156: 653-664 [Abstract] [Full Text]  
• Perez, F., Pernet-Gallay, K., Nizak, C., Goodson, H. V., Kreis, T. E., Goud, B. (2002). CLIPR-59, a new trans-Golgi/TGN cytoplasmic linker protein belonging to the CLIP-170 family. JCB 156: 631-642 [Abstract] [Full Text]  
• Mc Dermott, R., Ziylan, U., Spehner, D., Bausinger, H., Lipsker, D., Mommaas, M., Cazenave, J.-P., Raposo, G., Goud, B., de la Salle, H., Salamero, J., Hanau, D. (2002). Birbeck Granules Are Subdomains of Endosomal Recycling Compartment in Human Epidermal Langerhans Cells, Which Form Where Langerin Accumulates. Mol. Biol. Cell 13: 317-335 [Abstract] [Full Text]  
• van Dam, E. M., Stoorvogel, W. (2002). Dynamin-dependent Transferrin Receptor Recycling by Endosome-derived Clathrin-coated Vesicles. Mol. Biol. Cell 13: 169-182 [Abstract] [Full Text]  

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