The small GTP-binding protein rab4 controls an early sorting event on the endocytic pathway

Sluijs, Peter van der; Hull, Michael; Webster, Paul; Mâle, Philippe; Goud, Bruno; Mellman, Ira

doi:10.1016/0092-8674(92)90307-x

Cited by 595 publications

(455 citation statements)

References 48 publications

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“…Whereas the formation of H1-containing vesicles was not affected by depletion of rab5, it was strongly inhibited by the removal of rab4 ( Figure 7C). An involvement of rab4 in the generation of recycling vesicles is in agreement with previous observations in living cells (van der Sluijs et al, 1992).…”

Section: Rab4 and Rabaptin-5/rabex-5 Regulate The Formation Of Recyclsupporting

confidence: 92%

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In Vitro Formation of Recycling Vesicles from Endosomes Requires Adaptor Protein-1/Clathrin and Is Regulated by Rab4 and the Connector Rabaptin-5

Pagano

Crottet

Prescianotto-Baschong

et al. 2004

MBoC

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The involvement of clathrin and associated adaptor proteins in receptor recycling from endosomes back to the plasma membrane is controversial. We have used an in vitro assay to identify the molecular requirements for the formation of recycling vesicles. Cells expressing the asialoglycoprotein receptor H1, a typical recycling receptor, were surface biotinylated and then allowed to endocytose for 10 min. After stripping away surface-biotin, the cells were permeabilized and the cytosol washed away. In a temperature-, cytosol-, and nucleotide-dependent manner, the formation of sealed vesicles containing biotinylated H1 could be reconstituted. Vesicle formation was strongly inhibited upon immunodepletion of adaptor protein (AP)-1, but not of AP-2 or AP-3, from the cytosol, and was restored by readdition of purified AP-1. Vesicle formation was stimulated by supplemented clathrin, but inhibited by brefeldin A, consistent with the involvement of ARF1 and a brefeldin-sensitive guanine nucleotide exchange factor. The GTPase rab4, but not rab5, was required to generate endosome-derived vesicles. Depletion of rabaptin-5/rabex-5, a known interactor of both rab4 and ␥-adaptin, stimulated and addition of the purified protein strongly inhibited vesicle production. The results indicate that recycling is mediated by AP-1/clathrin-coated vesicles and regulated by rab4 and rabaptin-5/rabex-5. INTRODUCTIONEarly endosomes are a major sorting station for proteins and membranes in eukaryotic cells (Gruenberg, 2001;Maxfield and McGraw, 2004). They receive material from the cell surface by endocytosis and from the exocytic pathway via the trans-Golgi network (TGN), and they distribute it further to late endosomes and back to the TGN and the plasma membrane. Transport receptors like the transferrin receptor, the low-density lipoprotein (LDL) receptor, and the asialoglycoprotein (ASGP) receptor cycle continuously between the plasma membrane and early endosomes (Spiess, 1990;Trowbridge et al., 1993). Receptor-positive early endosomes can be subdivided into sorting endosomes and recycling endosomes (or endocytic recycling compartment, ERC). Primary endocytic vesicles fuse to sorting endosomes where ligands dissociate from their receptors because of a reduced internal pH. The receptors exit into tubular membranes that form recycling endosomes, whereas the ligands with the main fluid volume mature to late endosomes ("geometrybased sorting"; Maxfield and McGraw, 2004). There seem to be two main recycling pathways from early endosomes to the plasma membrane: a fast one directly from sorting endosomes and a slower one via recycling endosomes (Sheff et al., 1999;Hao and Maxfield, 2000;.The mechanisms to generate endosome-derived recycling vesicles are not clear, because there are seemingly contradictory findings. In general, formation of transport vesicles between organelles of the endocytic and secretory pathways requires cytosolic coat proteins to be recruited at the membrane of the donor compartment. Among the established coat complexes, clathr...

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Section: Rab4 and Rabaptin-5/rabex-5 Regulate The Formation Of Recyclsupporting

confidence: 92%

“…Three rab proteins have been implicated in regulating receptor recycling. Rab4 was implicated in regulating recycling from endosomes to the cell surface in nonpolarized and to the apical surface in polarized cells (van der Sluijs et al, 1992;Mohrmann et al, 2002;Deneka et al, 2003).…”

Section: Ap-1a/clathrin Coats Mediate Receptor Recyclingmentioning

confidence: 99%

In Vitro Formation of Recycling Vesicles from Endosomes Requires Adaptor Protein-1/Clathrin and Is Regulated by Rab4 and the Connector Rabaptin-5

Pagano

Crottet

Prescianotto-Baschong

et al. 2004

MBoC

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“…Secondly, transferrin receptors and Rab4 were found to associate with CFTR in subapical endosomes by immunogold electron microscopy in ductal epithelium of submandibular gland [5]. Whereas transferrin receptor is acknowledged as one of the most specific markers of recycling endosomes, rab4, a low-molecular-mass G-protein, has been proposed to regulate membrane traffic from early endosomes back to the plasma membrane [48]. Thirdly, if CFTRs were sorted to the late endosomes\lysosomes as opposed to recycling endosomes, taking into account the slow kinetics of transfer between early and late endosomes (t "/# l 17 min [47]), significant CFTR activity should have been detected with the functional assay upon inhibition of clathrin-dependent endocytosis.…”

Section: Discussionmentioning

confidence: 99%

Constitutive internalization of cystic fibrosis transmembrane conductance regulator occurs via clathrin-dependent endocytosis and is regulated by protein phosphorylation

Lukacs

Segal

Kartner

et al. 1997

Biochemical Journal

127

138

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Although the cystic fibrosis transmembrane conductance regulator (CFTR) is primarily implicated in the regulation of plasmamembrane chloride permeability, immunolocalization and functional studies indicate the presence of CFTR in the endosomal compartment. The mechanism of CFTR delivery from the cell surface to endosomes is not understood. To delineate the internalization pathway, both the rate and extent of CFTR accumulation in endosomes were monitored in stably transfected Chinese hamster ovary (CHO) cells. The role of clathrindependent endocytosis was assessed in cells exposed to hypertonic medium, potassium depletion or intracellular acid-load. These treatments inhibited clathrin-dependent endocytosis by 90 %, as verified by measurements of "#&I-transferrin uptake. Functional association of CFTR with newly formed endosomes was determined by an endosomal pH dissipation protocol [Lukacs, Chang, Kartner, Rotstein, Riordan and Grinstein (1992) J. Biol. Chem. 267, 14568-14572]. As a second approach, endocytosis of CFTR was determined after cell-surface biotinylation with the

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“…In mammalian cells, Rab4 and Rab11 have been implicated in recycling to the plasma membrane. Rab4 seems to be a regulator of fast transferrin receptor recycling, it is present mainly on early sorting endosomes, but absent from pericentriolar recycling endosomes (Daro et al 1996;van der Sluijs et al 1992). Rab11 localises to the pericentriolar recycling endosomes and regulates transport from the early sorting endosome to this compartment (Ullrich et al 1996).…”

Section: Is There Early Recycling In Dictyostelium Discoideum?mentioning

confidence: 99%

Molecular Mechanisms of Membrane Trafficking. What do we Learn from Dictyostelium discoideum?

Neuhaus

Soldati

1999

Protist

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The small GTP-binding protein rab4 controls an early sorting event on the endocytic pathway

Cited by 595 publications

References 48 publications

In Vitro Formation of Recycling Vesicles from Endosomes Requires Adaptor Protein-1/Clathrin and Is Regulated by Rab4 and the Connector Rabaptin-5

In Vitro Formation of Recycling Vesicles from Endosomes Requires Adaptor Protein-1/Clathrin and Is Regulated by Rab4 and the Connector Rabaptin-5

Constitutive internalization of cystic fibrosis transmembrane conductance regulator occurs via clathrin-dependent endocytosis and is regulated by protein phosphorylation

Molecular Mechanisms of Membrane Trafficking. What do we Learn from Dictyostelium discoideum?

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