A Rab1 mutant affecting guanine nucleotide exchange promotes disassembly of the Golgi apparatus.

Wilson, Bridget S.; Nuoffer, C; Meinkoth, Judy L.; McCaffery, Michael; Feramisco, James R.; Balch, William E.; Farquhar, Marilyn G.

doi:10.1083/jcb.125.3.557

Cited by 122 publications

(95 citation statements)

References 69 publications

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“…The above results underscore the highly dynamic nature of the Golgi complex revealed from studies with agents and conditions that cause it to disassemble and reassemble (including BFA, okadaic acid, IQ, and overexpression of ELP1 or mutant Rab la) (Lippincott-Schwartz et al, 1990;Lucocq et al, 1991;Hsu et al, 1992;Takizawa et al, 1993;Wilson et al, 1994) and from studies examining the distribution of Golgi enzymes during mitosis . It is of considerable interest, therefore, that the number of Golgi fragments that we report during nocodazole treatment (on average 250 per HeLa cell) is the same number Warren and colleagues found during mitosis in HeLa cells using quantitative electron microscopy (Lucocq et al, 1989).…”

Section: Discussionmentioning

confidence: 94%

Golgi dispersal during microtubule disruption: regeneration of Golgi stacks at peripheral endoplasmic reticulum exit sites.

Cole

Sciaky

Marotta

et al. 1996

MBoC

476

468

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Microtubule disruption has dramatic effects on the normal centrosomal localization of the Golgi complex, with Golgi elements remaining as competent functional units but undergoing a reversible "fragmentation" and dispersal throughout the cytoplasm. In this study we have analyzed this process using digital fluorescence image processing microscopy combined with biochemical and ultrastructural approaches. After microtubule depolymerization, Golgi membrane components were found to redistribute to a distinct number of peripheral sites that were not randomly distributed, but corresponded to sites of protein exit from the ER. Whereas Golgi enzymes redistributed gradually over several hours to these peripheral sites, ERGIC-53 (a protein which constitutively cycles between the ER and Golgi) redistributed rapidly (within 15 minutes) to these sites after first moving through the ER. Prior to this redistribution, Golgi enzyme processing of proteins exported from the ER was inhibited and only returned to normal levels after Golgi enzymes redistributed to peripheral ER exit sites where Golgi stacks were regenerated. Experiments examining the effects of microtubule disruption on the membrane pathways connecting the ER and Golgi suggested their potential role in the dispersal process. Whereas clustering of peripheral pre-Golgi elements into the centrosomal region failed to occur after microtubule disruption, Golgi-to-ER membrane recycling was only slightly inhibited. Moreover, conditions that impeded Golgi-to-ER recycling completely blocked Golgi fragmentation. Based on these findings we propose that a slow but constitutive flux of Golgi resident proteins through the same ER/Golgi cycling pathways as ERGIC-53 underlies Golgi Dispersal upon microtubule depolymerization. Both ERGIC-53 and Golgi proteins would accumulate at peripheral ER exit sites due to failure of membranes at these sites to cluster into the centrosomal region. Regeneration of Golgi stacks at these peripheral sites would re-establish secretory flow from the ER into the Golgi complex and result in Golgi dispersal.

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Section: Discussionmentioning

confidence: 94%

Golgi dispersal during microtubule disruption: regeneration of Golgi stacks at peripheral endoplasmic reticulum exit sites.

Cole

Sciaky

Marotta

et al. 1996

MBoC

476

468

View full text Add to dashboard Cite

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“…Cells transfected with S22N show Golgi disruption and relocation of Golgi proteins to perinuclear fragments. It is likely that those are analogous to Golgi elements induced in cells by microinjection of the S25N Rab1a mutant and shown by electron microscopic analysis to resemble polarized Golgi ministacks formed in the presence of nocodazole (Wilson et al, 1994). The COPII and COPI machinery is not noticeably perturbed in transfected cells.…”

Section: S22nmentioning

confidence: 91%

COPI Recruitment Is Modulated by a Rab1b-dependent Mechanism

Álvarez

Garcı́a-Mata

Brandon

et al. 2003

MBoC

123

127

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The small GTPase Rab1b is essential for endoplasmic reticulum (ER) to Golgi transport, but its exact function remains unclear. We have examined the effects of wild-type and three mutant forms of Rab1b in vivo. We show that the inactive form of Rab1b (the N121I mutant with impaired guanine nucleotide binding) blocks forward transport of cargo and induces Golgi disruption. The phenotype is analogous to that induced by brefeldin A (BFA): it causes resident Golgi proteins to relocate to the ER and induces redistribution of ER-Golgi intermediate compartment proteins to punctate structures. The COPII exit machinery seems to be functional in cells expressing the N121I mutant, but COPI is compromised, as shown by the release of ␤-COP into the cytosol. Our results suggest that Rab1b function influences COPI recruitment. In support of this, we show that the disruptive effects of N121I can be reversed by expressing known mediators of COPI recruitment, the GTPase ARF1 and its guanine nucleotide exchange factor GBF1. Further evidence is provided by the finding that cells expressing the active form of Rab1b (the Q67L mutant with impaired GTPase activity) are resistant to BFA. Our data suggest a novel role for Rab1b in ARF1-and GBF1-mediated COPI recruitment pathway.

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“…Rab1 is responsible for transporting vesicles from the ER to the Golgi. Disruption of Rab1 activity, by knockdown or overexpression of the dominant-negative Rab1S25N, results in fragmentation of the Golgi apparatus (36,37). We tested the effect of overexpression of nonphosphorylatable T75A and phosphomimetic T75E Rab1 on Golgi structure to determine if the T75 site was critical for Rab1 function.…”

Section: Resultsmentioning

confidence: 99%

Innate immunity kinase TAK1 phosphorylates Rab1 on a hotspot for posttranslational modifications by host and pathogen

Levin

Hertz

Burlingame

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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TGF-β activated kinase 1 (TAK1) is a critical signaling hub responsible for translating antigen binding signals to immune receptors for the activation of the AP-1 and NF-κB master transcriptional programs. Despite its importance, known substrates of TAK1 are limited to kinases of the MAPK and IKK families and include no direct effectors of biochemical processes. Here, we identify over 200 substrates of TAK1 using a chemical genetic kinase strategy. We validate phosphorylation of the dynamic switch II region of GTPase Rab1, a mediator of endoplasmic reticulum to Golgi vesicular transport, at T75 to be regulated by TAK1 in vivo. TAK1 preferentially phosphorylates the inactive (GDP-bound) state of Rab1. Phosphorylation of Rab1 disrupts interaction with GDP dissociation inhibitor 1 (GDI1), but not guanine exchange factor (GEF) or GTPaseactivating protein (GAP) enzymes, and is exclusive to membranelocalized Rab1, suggesting phosphorylation may stimulate Rab1 membrane association. Furthermore, we found phosphorylation of Rab1 at T75 to be essential for Rab1 function. Previous studies established that the pathogen Legionella pneumophila is capable of hijacking Rab1 function through posttranslational modifications of the switch II region. Here, we present evidence that Rab1 is regulated by the host in a similar fashion, and that the innate immunity kinase TAK1 and Legionella effectors compete to regulate Rab1 by switch II modifications during infection.

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A Rab1 mutant affecting guanine nucleotide exchange promotes disassembly of the Golgi apparatus.

Cited by 122 publications

References 69 publications

Golgi dispersal during microtubule disruption: regeneration of Golgi stacks at peripheral endoplasmic reticulum exit sites.

Golgi dispersal during microtubule disruption: regeneration of Golgi stacks at peripheral endoplasmic reticulum exit sites.

COPI Recruitment Is Modulated by a Rab1b-dependent Mechanism

Innate immunity kinase TAK1 phosphorylates Rab1 on a hotspot for posttranslational modifications by host and pathogen

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