Rab4 and Rab7 Define Distinct Nonoverlapping Endosomal Compartments

Bottger, Gina; Nagelkerken, Bas; Sluijs, Peter van der

doi:10.1074/jbc.271.46.29191

Cited by 77 publications

(64 citation statements)

References 33 publications

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“…Antibodies and Expression Constructs-Rabbit antibodies against rab4 and mouse monoclonal antibodies 9E10 and NH against the myc and influenza X31 NH epitope tags have been described previously (15,19,20). The rat monoclonal antibody against ZO-1 and rabbit antibodies against gp80 and EEA-1 were generously provided by Karl Matter (University of Geneva), Claudia Koch-Brandt (Johannes Gutenberg University, Mainz, Germany), and Michael Clague (University of Liverpool), respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Testifying to this notion is the recent discovery that the rab5 effector Vps34p differentially regulates endocytosis at the apical and basolateral surface in WIF-B cells (13). We have been investigating the role of rab4 in transport through the early endocytic pathway (14,15). rab4 is localized to early endocytic compartments and transport vesicles but not to the plasma membrane (16,17) and regulates recycling of cell surface receptors (14,18).…”

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rab4 Regulates Transport to the Apical Plasma Membrane in Madin-Darby Canine Kidney Cells

Mohrmann

Leijendekker

Gerez

et al. 2002

Journal of Biological Chemistry

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The small GTPase rab4 is associated with early endosomes and regulates membrane recycling in fibroblasts. rab4 is present in epithelial cells; however, neither its localization nor function has been established in this cell type. We transfected Madin-Darby canine kidney cells with rab4, the GTPase-deficient mutant rab4Q67L, and the dominant negative mutant rab4S22N that poorly binds guanine nucleotides. Confocal immunofluorescence microscopy showed that rab4 was concentrated on internal structures at the lateral side of the cell around the nucleus. Quantitative immunoelectron microscopy revealed that the majority of rab4 was localized in the upper third of the cytoplasm. In cell surface binding experiments with 125 I-transferrin, we found a redistribution of transferrin receptor from the basolateral to the apical plasma membrane in cells expressing rab4 and rab4Q67L. After accumulation of transferrin at 16°C in basolateral early endosomes, rab4 and rab4Q67L increased the amount of apically targeted transferrin receptor. A qualitatively similar effect was obtained in control cells treated with brefeldin A. The effects of brefeldin A and rab4 on apical targeting of transferrin receptor were not additive, suggesting that brefeldin A and rab4 may act in the same transport pathway from common endosomes.

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Section: Methodsmentioning

confidence: 99%

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rab4 Regulates Transport to the Apical Plasma Membrane in Madin-Darby Canine Kidney Cells

Mohrmann

Leijendekker

Gerez

et al. 2002

Journal of Biological Chemistry

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“…6C,b). On the contrary, the late endosomal marker Rab7 (Bottger et al, 1996;Bucci et al, 2000) (Fig. 6C,e) and the late endosomal and lysosomal marker lysosomeassociated membrane protein 3 (LAMP3) (Escola et al, 1998;Fukuda, 1991) (Fig.…”

Section: Ectopically Expressed Varp Protein Induces Giant Late Endosomentioning

confidence: 99%

Varp is a Rab21 guanine nucleotide exchange factor and regulates endosome dynamics

Zhang

Chen

2006

Journal of Cell Science

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Results Sequence information and expression pattern of VarpVarp was originally cloned in a yeast two-hybrid screen using the intracellular domain of human LRP6 as bait (X.Z. and Z.C., unpublished results). The full-length Varp protein, which is composed of 1050 and 1048 amino acids (aa) in human and mice, respectively, contains a VPS9 domain and eight ankyrin repeats. The Varp N-terminus shares significant homology to Rabex5, a well studied Rab5GEF (Fig. 1A), implying its function as a potential Rab5GEF. It has been reported that the four amino acids residues in Rabex5, Asp313, Pro317, Tyr354 and Thr357, which are conserved in all known Rab5GEFs, are crucial for the catalytic function on Rab5 and Rab21 (Delprato

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“…As shown in Figure 4, the hydrolysis of GTP to GDP was proportional to the relative concentration of the EVI5-GAP in the reaction. As a negative control, to demonstrate specific GAP activity of EVI5 toward Rab11, Rab4, which is also involved in endosome recycling (Bottger et al, 1996;Daro et al, 1996;Ward et al, 2005), was similarly cloned and expressed as a (His) 6 fusion protein and used in the GAP assay with EVI5N. The results shown in Figure 4 demonstrate that GTP hydrolysis occurs efficiently when EVI5N is included with Rab11 in the in vitro GTPase reaction.…”

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The EVI5 TBC domain provides the GTPase-activating protein motif for RAB11

et al. 2006

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The human EVI5 gene was originally isolated through its involvement with a constitutional chromosome translocation in a patient with stage 4S neuroblastoma. Recently, it has been shown that EVI5 is a centrosomal protein in interphase cells, which relocalizes to the midbody during late phases of mitosis. Disruption of its function leads to incomplete cell division and the formation of multinucleate cells. The EVI5 protein contains a TBC (TRE2/BUB/ CDC16 homology) motif located in the N-terminal region. Proteins containing a TBC domain have been shown in some cases to act as GTPase-activating proteins (GAPs) and function through the interaction with Rab-like small G proteins. Despite the identification of over 50 TBCcontaining proteins, and over 70 Rab-like proteins, only three combinations have been shown to have Rab/GAP activity to date. In this study, using linear ion trap mass spectroscopy, we have demonstrated that EVI5 exists in a protein complex with Rab11. Further, using a specific Rab-binding assay, we have shown that EVI5 preferentially interacts with the guanosine triphosphate-bound form of Rab11, and in a GAP activity assay, we have confirmed that EVI5 functions as a GAP for the Rab11 GTPase.Oncogene ( Proteins with homology to the so-called TBC domain, consisting of an B200-amino-acid motif initially identified in the TRE2/BUB2/CDC16 genes (Richardson and Zon, 1995), are considered to function as GTPaseactivating proteins (GAPs), partnering with Rab-like small G proteins. Rab GTPases are members of the Ras superfamily of guanosine triphosphate (GTP)-binding proteins that play critical roles in the regulation of important membrane and protein trafficking events in the cell. Many of the Rab proteins are associated with fundamental biological processes such as vesicle fusion, receptor recycling, membrane transport and cytokinesis (Zerial and McBride, 2001). There are, however, over 50 human proteins with predicted TBC domains, and over 70 human Rab proteins, of which only two TBC domain-containing proteins have so far been shown to demonstrably have Rab/GAP activity. The human EVI5 protein, which was identified at the breakpoint in a constitutional chromosome translocation in a patient with stage 4S neuroblastoma (Roberts et al., 1998), contains a TBC domain near its N terminus. EVI5 has been identified in the centrosome in interphase cells (Faitar et al., 2005) and in the midbody during the terminal stages of cytokinesis. Small interfering RNA knockdown of EVI5 results in multinucleate cells because of an inability of daughter cell abscission (Faitar et al., 2006). Because of the essential role of EVI5 in cytokinesis, as well as its implicated involvement in cancer development, we used a proteomics approach and identified the Rab protein that is activated by the EVI5 TBC domain.Rab proteins function by cycling between the biologically active GTP-bound form and the guanosine diphosphate (GDP)-bound inactive form. In the active GTP-bound conformation, these proteins can directly interact with specific eff...

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Rab4 and Rab7 Define Distinct Nonoverlapping Endosomal Compartments

Cited by 77 publications

References 33 publications

rab4 Regulates Transport to the Apical Plasma Membrane in Madin-Darby Canine Kidney Cells

rab4 Regulates Transport to the Apical Plasma Membrane in Madin-Darby Canine Kidney Cells

Varp is a Rab21 guanine nucleotide exchange factor and regulates endosome dynamics

The EVI5 TBC domain provides the GTPase-activating protein motif for RAB11

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