Abstract
Two endosome populations involved in recycling of membranes and receptors to the plasma membrane have been described, the early and the recycling endosome. However, this distinction is mainly based on the flow of cargo molecules and the spatial distribution of these membranes within the cell. To get insights into the membrane organization of the recycling pathway, we have studied Rab4, Rab5, and Rab11, three regulatory components of the transport machinery. Following transferrin as cargo molecule and GFP-tagged Rab proteins we could show that cargo moves through distinct domains on endosomes. These domains are occupied by different Rab proteins, revealing compartmentalization within the same continuous membrane. Endosomes are comprised of multiple combinations of Rab4, Rab5, and Rab11 domains that are dynamic but do not significantly intermix over time. Three major populations were observed: one that contains only Rab5, a second with Rab4 and Rab5, and a third containing Rab4 and Rab11. These membrane domains display differential pharmacological sensitivity, reflecting their biochemical and functional diversity. We propose that endosomes are organized as a mosaic of different Rab domains created through the recruitment of specific effector proteins, which cooperatively act to generate a restricted environment on the membrane.
References
53
Referenced
841
10.1083/jcb.91.3.716
/ J. Cell Biol. / Exocytosis of pinocytosed fluid in cultured cellskinetic evidence for rapid turnover and compartmentation by Besterman (1981)10.1016/0092-8674(93)90323-I
/ Cell / ADP-ribosylation factor, a small GTP-dependent regulatory protein stimulates phospholipase D activity by Brown (1993)10.1016/0092-8674(92)90306-W
/ Cell / The small GTPase rab5 functions as a regulatory factor in the early endocytic pathway by Bucci (1992)10.1152/ajpcell.1998.275.1.C163
/ Am. J. Physiol. / Rab11a redistributes to apical secretory canaliculus during stimulation of gastric parietal cells by Calhoun (1998)10.1091/mbc.9.11.3241
/ Mol. Biol. Cell / Rab11 is required for trans-Golgi network-to-plasma membrane transport and a preferential target for GDP dissociation inhibitor by Chen (1998)10.1038/17618
/ Nature. / The Rab5 effector EEA1 is a core component of endosome docking and fusion by Christoforidis (1999)10.1038/12075
/ Nat. Cell Biol. / Phosphoinositide-3-kinases are Rab5 effectors by Christoforidis (1999)10.1073/pnas.93.18.9559
/ Proc. Natl. Acad. Sci. USA / Rab4 and cellubrevin define different early endosome populations on the pathway of transferrin receptor recycling by Daro (1996)10.1038/360350a0
/ Nature / Brefeldin A inhibits Golgi membrane-catalyzed exchange of guanine nucleotide onto ARF protein by Donaldson (1992)10.1083/jcb.109.6.3303
/ J. Cell Biol / Iterative fractionation of recycling receptors from lysosomally destined ligands in an early sorting endosome by Dunn (1989)10.1126/science.279.5350.580
/ Science / Interaction of a Golgi-associated kinesin-like protein with Rab6 by Echard (1998)10.1083/jcb.128.4.549
/ J. Cell Biol. / Quantification of low-density lipoprotein and transferrin endocytic sorting in Hep2 cells by Ghosh (1994)10.1083/jcb.142.4.923
/ J. Cell Biol. / An endocytosed TGN38 chimeric protein is delivered to the TGN after trafficking through the endocytic recycling compartment in CHO cells by Ghosh (1998)10.1016/0092-8674(91)90316-Q
/ Cell / Rab5 controls early endosome fusion in vitro by Gorvel (1991)10.1083/jcb.109.6.2703
/ J. Cell Biol / A quantitative analysis of the endocytic pathway in baby hamster kidney cells by Griffiths (1989)10.1016/0955-0674(95)80013-1
/ Curr. Opin. Cell Biol. / Membrane transport in the endocytic pathway by Gruenberg (1995)10.1093/emboj/18.4.1071
/ EMBO (Eur. Mol. Biol. Organ.) J. / The exocyst is an effector for Sec4p, targeting secretory vesicles to sites of exocytosis by Guo (1999)10.1038/360352a0
/ Nature / Inhibition by brefeldin-A of a Golgi membrane enzyme that catalyzes exchange of guanine-nucleotide bound to ARF by Helms (1992)10.1016/0092-8674(83)90235-0
/ Cell / Intracellular routing of transferrin and transferrin receptors in epidermoid carcinoma A431 cells by Hopkins (1983)10.1038/346335a0
/ Nature / Movement of internalized ligand-receptor complexes along a continuous endosomal reticulum by Hopkins (1990)10.1074/jbc.270.19.11257
/ J. Biol. Chem. / A GDP/GTP exchange-stimulatory activity for the Rab5–RabGDI complex on clathrin-coated vesicles from bovine brain by Horiuchi (1995)10.1016/S0092-8674(00)80380-3
/ Cell / A novel Rab5 GDP/GTP exchange factor complexed to Rabaptin-5 links nucleotide exchange to effector recruitment and function by Horiuchi (1997)10.1083/jcb.137.3.563
/ J. Cell Biol / Two new ypt GTPases are required for exit from the yeast trans-golgi compartment by Jedd (1997)10.1016/0092-8674(91)90534-6
/ Cell / Brefeldin A's effects on endosomes, lysosomes, and the TGN suggest a general mechanism for regulating organelle structure and membrane traffic by Lippincott-Schwartz (1991)10.1242/jcs.107.12.3437
/ J. Cell Sci. / Cloning and subcellular localization of novel rab proteins reveals polarized and cell-type specific expression by Lütcke (1994)10.1083/jcb.121.6.1257
/ J. Cell Biol / Sorting of membrane components from endosomes and subsequent recycling to the cell surface occurs by a bulk flow process by Mayor (1993)10.1016/S0092-8674(00)81966-2
/ Cell / Oligomeric complexes link Rab5 effectors with NSF and drive membrane fusion via interactions between EEA1 and syntaxin13 by McBride (1999)10.1016/S0960-9822(98)70018-1
/ Curr. Biol / A novel role for Rab5-GDI in ligand sequestration into clathrin-coated pits by McLauchlan (1998)10.1146/annurev.cellbio.12.1.575
/ Annu. Rev. Cell Dev. Biol. / Endocytosis and molecular sorting by Mellman (1996)10.1016/S0960-9822(07)00351-X
/ Curr. Biol. / Involvement of the endosomal autoantigen EEA1 in homotypic fusion of early endosomes by Mills (1998)10.1074/jbc.270.22.13503
/ J. Biol. Chem. / EEA1, an early endosome-associated protein by Mu (1995)10.1038/14075
/ Nat. Cell Biol. / Rab5 regulates motility of early endosomes on microtubules by Nielsen (1999)10.1016/S0955-0674(97)80025-7
/ Curr. Opin. Cell Biol. / The diversity of Rab proteins in vesicle transport by Novick (1997)10.1242/jcs.106.4.1249
/ J. Cell Sci / Molecular cloning and subcellular localization of 3 GTP-binding proteins of the rab subfamily by Olkkonen (1993)10.1073/pnas.94.14.7326
/ Proc. Natl. Acad. Sci. USA / Identification of an early endosomal protein regulated by phosphatidylinositol 3-kinase by Patki (1997)10.1016/0955-0674(94)90071-X
/ Curr. Opin. Cell Biol. / Rab GTPasesmaster regulators of membrane trafficking by Pfeffer (1994)10.1073/pnas.95.11.6187
/ Proc. Natl. Acad. Sci. USA / Hydrolysis of GTP on rab11 is required for the direct delivery of transferrin from the pericentriolar recycling compartment to the cell surface but not from sorting endosomes by Ren (1998)10.1016/0092-8674(88)90532-6
/ Cell / Two distinct subpopulations of endosomes involved in membrane recycling and transport to lysosomes by Schmid (1988)10.1126/science.8385367
/ Science / Phosphatidylinositol 3-kinase encoded by yeast VPS34 gene essential for protein sorting by Schu (1993)10.1083/jcb.145.1.123
/ J. Cell Biol. / The recycling pathway contains two distinct populations of early endosomes with different sorting functions by Sheff (1999)10.1038/28879
/ Nature / EEA1 links phosphatidylinositol 3-kinase function to Rab5 regulation of endosome fusion by Simonsen (1998)10.1073/pnas.84.20.7119
/ Proc. Natl. Acad. Sci. USA / High resolution acidification kinetics of transferrin in Balb/c 3T3 cellsexposure to pH 6 followed by temperature-sensitive alkalization during recycling by Sipe (1987)10.1091/mbc.7.3.355
/ Mol. Biol. Cell / Wortmannin alters the transferrin receptor endocytic pathway in vivo and in vitro by Spiro (1996)10.1083/jcb.132.1.21
/ J. Cell Biol / A novel class of clathrin-coated vesicles budding from endosomes by Stoorvogel (1996)10.1083/jcb.118.4.813
/ J. Cell Biol. / In AtT20 and HeLa cells brefeldin A induces the fusion of tubular endosomes and changes their distribution and some of their endocytic properties by Tooze (1992)10.1242/jcs.112.24.4773
/ J. Cell Sci. / Biochemical analysis of distinct Rab5- and Rab11-positive endosomes along the transferrin pathway by Trischler (1999)10.1083/jcb.135.4.913
/ J. Cell Biol. / Rab11 regulates recycling through the pericentriolar recycling endosome by Ullrich (1996)10.1016/0014-5793(93)81707-7
/ FEBS Lett. / Rab11, a small GTPase associated with both constitutive and regulated secretory pathways in PC12 cells by Urbe (1993)10.1016/0092-8674(92)90307-X
/ Cell / The small GTP-binding protein rab4 controls an early sorting event on the endocytic pathway by Van der Sluijs (1992)10.1093/emboj/17.7.1941
/ EMBO (Eur. Mol. Biol. Organ.) J. / Distinct Rab-binding domains mediate the interaction of Rabaptin-5 with GTP-bound rab4 and rab5 by Vitale (1998)10.1083/jcb.143.6.1505
/ J. Cell Biol. / Recycling of Golgi resident glycosyltransferases through the ER reveals a novel pathway and provides an explanation for nocodazole-induced Golgi scattering by White (1998)10.1016/0092-8674(84)90414-8
/ Cell / Segregation of transferrin to a mildly acidic (pH 6.5) para-Golgi compartment in the recycling pathway by Yamashiro (1984)10.1083/jcb.140.5.1039
/ J. Cell Biol / Rab17 regulates membrane trafficking through apical recycling endosomes in polarized epithelial cells by Zacchi (1998)
Dates
Type | When |
---|---|
Created | 23 years ago (July 26, 2002, 12:45 p.m.) |
Deposited | 2 years, 1 month ago (July 22, 2023, 7:05 a.m.) |
Indexed | 5 days, 1 hour ago (Aug. 20, 2025, 8:26 a.m.) |
Issued | 25 years, 3 months ago (May 15, 2000) |
Published | 25 years, 3 months ago (May 15, 2000) |
Published Online | 25 years, 3 months ago (May 15, 2000) |
Published Print | 25 years, 3 months ago (May 15, 2000) |
@article{S_nnichsen_2000, title={Distinct Membrane Domains on Endosomes in the Recycling Pathway Visualized by Multicolor Imaging of Rab4, Rab5, and Rab11}, volume={149}, ISSN={1540-8140}, url={http://dx.doi.org/10.1083/jcb.149.4.901}, DOI={10.1083/jcb.149.4.901}, number={4}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Sönnichsen, Birte and De Renzis, Stefano and Nielsen, Erik and Rietdorf, Jens and Zerial, Marino}, year={2000}, month=may, pages={901–914} }