Brefeldin A Inhibited Activity of the Sec7 Domain of p200, a Mammalian Guanine Nucleotide-exchange Protein for ADP-ribosylation Factors

Morinaga, Naoko; Adamik, Ronald; Moss, Joel; Vaughan, Martha

doi:10.1074/jbc.274.25.17417

Cited by 46 publications

(35 citation statements)

References 30 publications

(42 reference statements)

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“…PDE3A depletion did not alter total ARF1, 5, or 6, but recovery of active ARF1 was significantly lower, whereas amounts of active ARF5 (class II) and ARF6 (class III) were unchanged. These results, and previous data (8,27), confirm a specificity of endogenous intracellular BIG1 and BIG2 for class I ARFs, despite a sometimes apparent lack of ARF specificity of GEP activity of the highly conserved Sec 7 domains from different GEPs when assayed in vitro (28).…”

Section: Discussionsupporting

confidence: 74%

Interaction of phosphodiesterase 3A with brefeldin A-inhibited guanine nucleotide-exchange proteins BIG1 and BIG2 and effect on ARF1 activity

Puxeddu

Uhart

et al. 2009

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

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ADP-ribosylation factors (ARFs) have crucial roles in vesicular trafficking. Brefeldin A-inhibited guanine nucleotide-exchange proteins (BIG)1 and BIG2 catalyze the activation of class I ARFs by accelerating replacement of bound GDP with GTP. Several additional and differing actions of BIG1 and BIG2 have been described. These include the presence in BIG2 of 3 A kinase-anchoring protein (AKAP) domains, one of which is identical in BIG1. Proteins that contain AKAP sequences act as scaffolds for the assembly of PKA with other enzymes, substrates, and regulators in complexes that constitute molecular machines for the reception, transduction, and integration of signals from cAMP or other sources, which are initiated, propagated, and transmitted by chemical, electrical, or mechanical means. Specific depletion of HeLa cell PDE3A with small interfering RNA significantly decreased membrane-associated BIG1 and BIG2, which by confocal immunofluorescence microscopy were widely dispersed from an initial perinuclear Golgi concentration. Concurrently, activated ARF1-GTP was significantly decreased. Selective inhibition of PDE3A by 1-h incubation of cells with cilostamide similarly decreased membrane-associated BIG1. We suggest that decreasing PDE3A allowed cAMP to accumulate in microdomains where its enzymatic activity limited cAMP concentration. There, cAMP-activated PKA phosphorylated BIG1 and BIG2 (AKAPs for assembly of PKA, PDE3A, and other molecules), which decreased their GEP activity and thereby amounts of activated ARF1-GTP. Thus, PDE3A in these BIG1 and BIG2 AKAP complexes may contribute to the regulation of ARF function via limitation of cAMP effects with spatial and temporal specificity.A DP-ribosylation factors (ARFs) are members of the Ras superfamily of Ϸ20-kDa GTPases that have diverse roles in intracellular vesicular trafficking. ARF binding to donor membranes initiates the formation of vesicles for regulated translocation of protein and lipid molecules among eukaryotic cell organelles. This action requires cycling between inactive, largely cytosolic ARF-GDP, and GTP-bound active, membraneassociated forms (1-3). Conversion of ARF-GDP to ARF-GTP is catalyzed by guanine nucleotide-exchange proteins (GEPs), which accelerate the release of bound GDP to permit GTP binding. All known GEPs, although they differ in molecular size and structure, share a highly conserved central sequence of Ϸ200 aa, the Sec7 domain, that is responsible for this function (4-5). Sensitivity of GEP activity to inhibition by brefeldin A (BFA), a fungal fatty acid metabolite that blocks protein secretion (6), distinguishes 2 major groups. BFA-inhibited GEP (BIG)1 (Ϸ200 kDa) and BIG2 (Ϸ190 kDa) were first purified together in Ͼ670-kDa multiprotein complexes from bovine brain cytosol, based on assays of BFA-inhibited ARF activation (7). The molecules are 74% identical in overall amino acid sequences, with 90% identity in Sec7 and other domains (8). Systematic yeast 2-hybrid screening was used to identify their potentially functional interaction...

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Section: Discussionsupporting

confidence: 74%

Interaction of phosphodiesterase 3A with brefeldin A-inhibited guanine nucleotide-exchange proteins BIG1 and BIG2 and effect on ARF1 activity

Puxeddu

Uhart

et al. 2009

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

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“…7c) as observed in the presence of Arf1[T31N] (Fig. 6A, c1-c4), suggesting that, as in animal cells, Arf1 may play a role in the trafficking of H ϩ -ATPase:GFP to the plasma membrane through a BFA-sensitive factor (Sata et al, 1998;Morinaga et al, 1999).…”

Section: Arf1[t31n] May Cause Fusion Of the Golgi Membranes To The Ermentioning

confidence: 70%

“…In animal cells, BFA and the dominant negative mutant of Arf1 have been shown to have similar effects on intracellular trafficking (Sata et al, 1998;Morinaga et al, 1999). BFA has also been shown to inhibit intracellular trafficking in plant cells (Gomez and Chrispeels, 1993;Boevink et al, 1999).…”

Section: Arf1[t31n] May Cause Fusion Of the Golgi Membranes To The Ermentioning

confidence: 99%

ADP-Ribosylation Factor 1 of Arabidopsis Plays a Critical Role in Intracellular Trafficking and Maintenance of Endoplasmic Reticulum Morphology in Arabidopsis

Lee¹,

Min

Lee³

et al. 2002

Plant Physiology

120

126

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ADP-ribosylation factors (Arf), a family of small GTP-binding proteins, play important roles in intracellular trafficking in animal and yeast cells. Here, we investigated the roles of two Arf homologs, Arf1 and Arf3 of Arabidopsis, in intracellular trafficking in plant cells. We generated dominant negative mutant forms of Arf 1 and Arf3 and examined their effect on trafficking of reporter proteins in protoplasts. Arf1[T31N] inhibited trafficking of H ϩ -ATPase:green fluorescent protein (GFP) and sialyltransferase (ST):GFP to the plasma membrane and the Golgi apparatus. In addition, Arf1[T31N] caused relocalization of the Golgi reporter protein ST:GFP to the endoplasmic reticulum (ER). In protoplasts expressing Arf1[T31N], ST:red fluorescent protein remained in the ER, whereas H ϩ -ATPase:GFP was mistargeted to another organelle. Also, expression of Arf1[T31N] in protoplasts resulted in profound changes in the morphology of the ER. The treatment of protoplasts with brefeldin A had exactly the same effect as Arf1[T31N] on various intracellular trafficking pathways. In contrast, Arf3[T31N] did not affect trafficking of any of these reporter proteins. Inhibition experiments using mutants with various domains swapped between Arf1 and Arf3 revealed that the N-terminal domain is interchangeable for trafficking inhibition. However, in addition to the T31N mutation, motifs in domains II, III, and IV of Arf1 were necessary for inhibition of trafficking of H ϩ -ATPase:GFP. Together, these results strongly suggest that Arf1 plays a role in the intracellular trafficking of cargo proteins in Arabidopsis, and that Arf1 functions through a brefeldin A-sensitive factor.In eukaryotic cells, a large number of proteins are transported to their final destination after translation by a process called intracellular trafficking. The mechanism of intracellular trafficking has been extensively studied in animal, plant, and yeast cells. Based on numerous studies, the general mechanism of intracellular trafficking is thought to be similar in various organisms (Rothman, 1994; Jahn and Sü dhof, 1999; Bassham and Raikhel, 2000), implying that the fundamental aspects of intracellular trafficking between the endoplasmic reticulum (ER), Golgi apparatus, vacuole, and plasma membrane are similar in plant cells as well. In fact, many plant proteins have been shown to complement mutations in corresponding proteins in yeast cells (Bassham et al., 1995; Takeuchi et al., 1998). Also, proteins such as clathrin, coatomer subunits of coat protein I (COPI) vesicles, and many small GTP-binding proteins have been identified in plant cells (Memon et al., 1993; Regad et al., 1993; Lebas and Axelos, 1994; Blackbourn and Jackson, 1996; Contreras et al., 2000), although in most cases, the exact biological roles of these proteins have not been directly addressed. However, differences in trafficking also exist between plant and animal cells. It has recently been shown that plant cells have at least two different types of vacuoles: the lytic and storage vacuoles...

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“…A candidate is BFA, which inhibits vesicular traffic from the Golgi apparatus by slowing GDP-GTP exchange on ADPribosylation factors (ARF); the latter are targets of GEFs for ARF that are structurally related to Epac, although they are not activated by cAMP (Morinaga et al, 1996(Morinaga et al, , 1999Chardin and McCormick, 1999). We found that BFA also antagonizes 8-CPT action on synaptic transmission, presumably by similarly blocking a downstream action of Epac.…”

Section: A New Epac Antagonistmentioning

confidence: 99%

cAMP Acts on Exchange Protein Activated by cAMP/cAMP-Regulated Guanine Nucleotide Exchange Protein to Regulate Transmitter Release at the Crayfish Neuromuscular Junction

Zhong

Zucker²

2005

J. Neurosci.

102

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Glutamatergic synapses are highly modifiable, suiting them for key roles in processes such as learning and memory. At crayfish glutamatergic neuromuscular junctions, hyperpolarization and cyclic nucleotide-activated (HCN) ion channels mediate hormonal modulation of glutamatergic synapses and a form activity-dependent long-term facilitation (LTF) of synaptic transmission. Here, we show that a new target for cAMP, exchange protein activated by cAMP (Epac) or cAMP-regulated guanine nucleotide exchange protein, is involved in the hormonal enhancement of synaptic transmission by serotonin. Induction of LTF "tags" synapses, rendering them responsive to cAMP in an HCN-independent manner. Epac also mediates the enhancement of tagged synapses. Thus, the cAMP-dependent enhancement of transmission is mediated by two separate pathways, neither of which involves protein kinase A.

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Brefeldin A Inhibited Activity of the Sec7 Domain of p200, a Mammalian Guanine Nucleotide-exchange Protein for ADP-ribosylation Factors

Cited by 46 publications

References 30 publications

Interaction of phosphodiesterase 3A with brefeldin A-inhibited guanine nucleotide-exchange proteins BIG1 and BIG2 and effect on ARF1 activity

Interaction of phosphodiesterase 3A with brefeldin A-inhibited guanine nucleotide-exchange proteins BIG1 and BIG2 and effect on ARF1 activity

ADP-Ribosylation Factor 1 of Arabidopsis Plays a Critical Role in Intracellular Trafficking and Maintenance of Endoplasmic Reticulum Morphology in Arabidopsis

cAMP Acts on Exchange Protein Activated by cAMP/cAMP-Regulated Guanine Nucleotide Exchange Protein to Regulate Transmitter Release at the Crayfish Neuromuscular Junction

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