Distinct Membrane Domains on Endosomes in the Recycling Pathway Visualized by Multicolor Imaging of Rab4, Rab5, and Rab11

By B. Sönnichsen, Stefano De Renzis, E. Nielsen, J. Rietdorf, Marino Zerial. Journal of Cell Biology, 2000

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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.

Subfields: Cell Biology, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/e86df7d269c1ef57413dd4842e364f3ac3e5e992

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Citations in the corpus

Rab GTPases as coordinators of vesicle traffic (2009, background): “Later studies, using low levels of overexpressed green fluorescent protein-tagged endosomal Rab GTPases, have shown that even different Rab proteins localized on the same organelle occupy distinct membrane microdomains, which are sometimes referred to as Rab domain”
Subcellular targeting strategies for drug design and delivery (2010, background): “One route involves RAB4 in direct sorting of the cargo from the endosomes to the plasma membran”
Pathways and mechanisms of endocytic recycling (2009, positive): “Evidence of this transformation has come from live imaging studies, showing that the early endosome loses RAB5 and acquires RAB11 (Ref”
The endocytic pathway: a mosaic of domains (2001, background): “cgi?l=8766">Rab11 , show a distinct, but partially overlapping, distribution in vivo , which presumably corresponds to different effector platform”
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GPI-anchored proteins are delivered to recycling endosomes via a distinct cdc42-regulated, clathrin-independent pinocytic pathway. (2002, background): “GFP-rab4 and rab5 colocalize with Tf in sorting endosomes at these times (data not shown; Sonnichsen et al., 2000).”
The Phagosome Proteome (2001, background): “, 1999), while the association of Rab4 and Rab11 with recycling endosomes (Sheff et al., 1999; Sonnichsen et al., 2000) suggests that recycling processes might also be important for phagolysosome biogenesis.”
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Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes (2006, background): “GFP-fusions of the early endosomal Rab proteins, GFP-Rab4, GFP-Rab5 and GFP-Rab11 (Sonnichsen et al., 2000), showed no colocalization with mAtg9 (data not shown).”
SORTING IT OUT: REGULATION OF EXOSOME LOADING (2014, background): “Rab proteins reversibly associate with membranes via geranylgeranyl modifications and localize at different membrane-bound compartments, where they regulate sequential steps in membrane traffic—such as vesicle budding, transport, tethering, and fusion—through cycling between an active GTP-bound form”
Membrane fatty acid transporters as regulators of lipid metabolism: implications for metabolic disease. (2010, background): “Interestingly, Rab4 and Rab11 seem to be differentially localized: Rab4 is predominantly localized in a specialized insulin-responsive preendosomal compartment uniquely dedicated to the storage of GLUT4 (452), whereas Rab11 specifically associates with recycling endosomes in mammalian cell lines (39”
Rab proteins as membrane organizers (2001, background): “cgi?Q=rab11a%20or%20rab11b&ORG=Hs"> Rab11 tagged with GREEN FLUORESCENT PROTEIN (GFP) have also revealed compartmentalization of these three GTPases within the endosomal membran”
Rab conversion as a mechanism of progression from early to late endosomes. (2005, methodology): “Rab Domains Undergo Assembly and Disassembly Rab GTPases organize the endocytic pathway into a mosaic of biochemically and functionally distinct membrane domains (Barbero et al., 2002; Sonnichsen et al., 2000).”