Distinct Rab-binding domains mediate the interaction of Rabaptin-5 with GTP-bound rab4 and rab5

Vitale, Gaetano; Rybin, Vladimir; Christoforidis, Savvas; Thornqvist, Per Öve; McCaffrey, Mary W.; Stenmark, Harald; Zerial, Marino

doi:10.1093/emboj/17.7.1941

Cited by 212 publications

(233 citation statements)

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“…To test the specificity of Rab5 involvement, we also examined Rab4, which mediates receptor recycling between early endosomes and the plasma membrane. Rabaptin-5 binds to the active form of Rab4 at its N terminus (25). As shown in Fig.…”

Section: Gsk-3 Regulation Of Ampars Involves the Stimulation Of The Gmentioning

confidence: 98%

Regulation of AMPA Receptor Trafficking and Function by Glycogen Synthase Kinase 3

Wei

Liu

Yan

2010

Journal of Biological Chemistry

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Accumulating evidence suggests that glycogen synthase kinase 3 (GSK-3) is a multifunctional kinase implicated in neuronal development, mood stabilization, and neurodegeneration. However, the synaptic actions of GSK-3 are largely unknown. In this study, we examined the impact of GSK-3 on AMPA receptor (AMPAR) channels, the major mediator of excitatory transmission, in cortical neurons. Application of GSK-3 inhibitors or knockdown of GSK-3 caused a significant reduction of the amplitude of miniature excitatory postsynaptic current (mEPSC), a readout of the unitary strength of synaptic AMPARs. Treatment with GSK-3 inhibitors also decreased surface and synaptic GluR1 clusters on dendrites and increased internalized GluR1 in cortical cultures. Rab5, the small GTPase controlling the transport from plasma membrane to early endosomes, was activated by GSK-3 inhibitors. Knockdown of Rab5 prevented GSK-3 inhibitors from regulating mEPSC amplitude. Guanyl nucleotide dissociation inhibitor (GDI), which regulates the cycle of Rab5 between membrane and cytosol, formed an increased complex with Rab5 after treatment with GSK-3 inhibitors. Blocking the function of GDI occluded the effect of GSK-3 inhibitors on mEPSC amplitude. In cells transfected with the non-phosphorylatable GDI mutant, GDI(S45A), GSK-3 inhibitors lost the capability to regulate GDI-Rab5 complex, mEPSC amplitude, and AMPAR surface expression. These results suggest that GSK-3, via altering the GDI-Rab5 complex, regulates Rab5-mediated endocytosis of AMPARs. It provides a potential mechanism underlying the role of GSK-3 in synaptic transmission and plasticity.Glycogen synthase kinase 3 (GSK-3), 3 which was initially identified as an enzyme that regulates glycogen synthesis in response to insulin (1), has emerged as a multifunctional serine/ threonine kinase involved in many cellular processes, including the proliferation, differentiation, cell adhesion, cell survival and apoptotic signaling, axon growth, neuronal polarity, and neural progenitor homeostasis during development (2-6). There are two closely related GSK-3 isoforms, GSK-3␣ and GSK-3␤, and they are highly enriched in the brain (7). GSK-3 is usually active in resting cells, and its activity can be inhibited by Akt-mediated phosphorylation at N-terminal serine residues (8).GSK-3 has been implicated in mood disorders (9) because it is the main target of lithium (10), the most effective treatment for manic-depressive illness. Convergent evidence also suggests that impaired Akt-GSK-3␤ signaling contributes to schizophrenia pathogenesis (11). Moreover, inhibition of GSK-3 has been found to reduce the production of ␤-amyloid peptides (12) and the hyperphosphorylation of Tau protein (13), two key events in the etiology of Alzheimer disease. Although pharmacological inhibitors of GSK-3 offer great potential for the treatment of a variety of neurological disorders (14), it is important to know the molecular targets and physiological function of GSK-3 in central neurons.Our previous study has found that the NMDA ...

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Section: Gsk-3 Regulation Of Ampars Involves the Stimulation Of The Gmentioning

confidence: 98%

Regulation of AMPA Receptor Trafficking and Function by Glycogen Synthase Kinase 3

Wei

Liu

Yan

2010

Journal of Biological Chemistry

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“…Initially, rabaptin-5 was identified as an interactor of rab5 (Stenmark et al, 1995) and rabex-5 as a rab5 guanine nucleotide exchange factor (Horiuchi et al, 1997). Rabaptin-5 in addition was shown to bind to rab4 and AP-1 (Vitale et al, 1998;de Renzis et al, 2002;Deneka et al, 2003). On immunodepletion of rabaptin-5/rabex-5 from the cytosol with an anti-rabaptin-5 antibody ( Figure 8A), formation of endosomal vesicles was reproducibly stimulated (Figure 8B), suggesting an inhibitory role of the complex.…”

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

confidence: 98%

“…Rabenosyn-5 and rabaptin-5/rabex-5 have been shown to be interaction partners of rab4 as well as rab5 (Vitale et al, 1998;de Renzis et al, 2002). The fact that these proteins can simultaneously bind to both active rab GTPases suggested that they regulate endosomal protein sorting and recycling by defining and connecting endosomal subdomains (de Renzis et al, 2002).…”

Section: In Vitro Formation Of Recycling Vesiclesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…In addition, brefeldin A (BFA), an inhibitor of guanine nucleotide exchange factors of the GTPase ADPribosylation factor 1 (ARF1) involved in recruiting AP-1-and AP-3-containing coats, partially inhibited transferrin receptor recycling in nonpolarized cells . Overexpression of rabaptin-5, an interactor of the ␥-subunit of AP-1 (Hirst et al, 2000;Shiba et al, 2002) as well as of rab4 and rab5 (Vitale et al, 1998), was shown to inhibit transferrin receptor recycling, unless ␥-adaptin was overexpressed simultaneously (Deneka et al, 2003).AP-1/clathrin coats on endosomes may, however, be involved in other functions than recycling to the plasma membrane (Hinners and Tooze, 2003) is transported via endosomes to the Golgi, was found to be colocalized in recycling endosomes with AP-1 and clathrin and accumulated in transferrin receptor-positive endosomes upon BFA treatment (Mallard et al, 1998). In cells lacking the 1A subunit of AP-1, the mannose-6-phosphate receptor was found to accumulate in endosomes, rather than in the TGN, supporting an AP-1-dependent pathway from endosomes to the TGN (Meyer et al, 2000).…”

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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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Regulators of membrane trafficking andMycobacterium tuberculosis phagosome maturation block

et al. 2000

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The biogenesis and maturation of phagosomes is an area of study which has been employing aspects of proteomic analyses and variations on that theme by identifying components on isolated organelles and following their dynamic changes and interactions with the endocytic pathway. In the case of Mycobacterium tuberculosis phagosome, the arrest of its maturation in infected macrophages, referred to in classical texts as the inhibition of phagosome-lysosome fusion, represents a phenomenon that is used to functionally dissect the phagosomal maturation pathway. In this review, we summarize the recent studies on regulators of membrane trafficking and other organelle components in the context of phagosomal biogenesis and mycobacterial phagosome maturation arrest.

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Distinct Rab-binding domains mediate the interaction of Rabaptin-5 with GTP-bound rab4 and rab5

Cited by 212 publications

References 42 publications

Regulation of AMPA Receptor Trafficking and Function by Glycogen Synthase Kinase 3

Regulation of AMPA Receptor Trafficking and Function by Glycogen Synthase Kinase 3

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

Regulators of membrane trafficking andMycobacterium tuberculosis phagosome maturation block

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